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1.  PA02.06. Tracking the transitions in Guggulu Kalpana : An extensive review through Brihat Trayi and Laghu Trayi 
Ancient Science of Life  2013;32(Suppl 2):S51.
Purpose:
Guggulu Kalpana enjoys a coveted position in the arena of Ayurvedic therapeutics. Guggulu Kalpana is widely used in Charak Samhita & Sushruta Samhita and its notable collection is described in Ashtanga Sangraha. Out of laghu trayi, Sharangadhara Samhita has described Guggulu kalpas at length. Though its present form is closely related to Guti Vati Kalpana, it has not been the case always. Present study was attempted to track these transitions in Guggulu Kalpana during period of Brihat Trayi and Laghu Trayi and propose the importance of this journey in the view of current Ayurvedic pharmaceutics and therapeutics.
Method:
A comprehensive review of Brihat Trayi and Laghu Trayi was done. Opinions of their critics as well as contemporaries were also taken into consideration. These views were collated on the basis of current trends and researches in Guggulu Kalpana.
Result:
Amongst other categories, main usage of Guggulu Kalpana was seen in form of Kwatha and Guti Vati Kalpana. Though used in great deal, Brihat Trayi doesn’t describe Guggulu in every respect. Different point of view regarding preparation of Guggulu Kalpana was observed in all these treatises. Various functional limitations and constant improvisations seemed to have shaped the Guggulu Kalpana in its today's form.
Conclusion:
Current status of Ayurvedic pharmaceutics in general and Guggulu Kalpana in particular, is greatly influenced by Sharangadhara Samhita. It mainly shows use of Guggulu in GutiVati form. The Brihat Trayi treatises, however display its use in Conjunction of Kwatha Kalpana chiefly. This paradigm shift in the pharmaceutics of Guggulu Kalpana highlights the buoyant and pliant nature of Ayurveda. The difference in choice of kalpana is explained on the basis of soluble alkaloid content and insoluble resinous gum content of Guggulu. Thus, this study is helpful to understand the progression of Ayurvedic therapeutics and prospective avenues for its advancement.
doi:10.4103/0257-7941.123867
PMCID: PMC4147523
2.  Mahayograj guggulu: Heavy metal estimation and safety studies 
Objective:
This study was conducted to estimate the heavy metal profile and determine the safety of Mahayograj guggulu, an Ayurvedic herbo-mineral preparation.
Design:
Mahayograj guggulu, manufactured by Shree Baidynath Ayurved Bhawan Pvt. Ltd., Gwalior Road, Jhansi - 284 003 (of batch number-07 and manufacturing date October 2004) was procured from the local market. Heavy metal concentrations were measured using an atomic absorption spectrophotometer. A total of 40 Charles Foster strain albino rats of either sex with an average body weight of 160–250 g were divided into four groups (Groups I, II, III and IV), with 10 animals in each group. Group I served as the control, while Group II, III and IV rats received Mahayograj guggulu at a dose of 54 (dose equivalent to human therapeutic dose), 270 (five-times the dose equivalent to the human therapeutic dose) and 540 (10-times the dose equivalent to human therapeutic dose) mg/kg, p.o. for 120 days. The effect of drug administration was noted on the ponderal, biochemical, hematological and histopathological parameters. In addition, urine examination was also carried out. At the end of the study, only six rats per group were sacrificed as per the IAEC advice.
Results:
Mahayograj guggulu was found to be safe at all dose levels tested. No significant behavioral changes were noted in any of the groups studied. The effect on food and water consumption and fecal and urine output remained unaffected in all groups during the study period. No major alterations were observed in hematology, serum biochemistry, necropsy and histopathology at the therapeutically advocated dose level. Heavy metal content measurement indicated levels of 25.8 µg/g for lead, 0.07 µg/g for mercury and 5.19 µg/g for arsenic.
Conclusions:
The test drug is well tolerated as no changes of a serious nature could be observed in any of the parameters assessed.
doi:10.4103/0974-7788.72486
PMCID: PMC2996572  PMID: 21170206
Heavy metal content; Mahayograj guggulu; safety; toxicity
3.  OA03.11. A comparative study of guggulu chitrak kshar – sutra and snuhi apamarg kshar – sutra in the management of fistula in ano 
Ancient Science of Life  2013;32(Suppl 2):S34.
Purpose:
Fistula in ano is a condition which has been recognized as difficult surgical diseases in all the ancient and modern medical sciences of the world. In Ayurvedic texts fistulainano is described as Bhagandar. This disease is recurrent in nature which makes it more difficult for treatment. So it produces inconvenience in routine life. KsharSutra has been proved as a big revolution in the treatment of fistulainano. It is the need to do further researches to get more efficient Kshar Sutra.
Method:
The present study was clinical, randomised, single blind trial. In the present research work Guggulu Chitraka KsharSutra has been taken for comparative study wth snuhi apamarga ksharsutra. Thirty patients cases of fistulainano were selected from OPD/IPD of Shalya Tantra department of National Institute of Ayurveda, Jaipur. Total patients were divided into two equal groups. The patients of group A were treated with Snuhi Apamarga KsharSutra and the patients of group B were treated with Guggulu Chitraka KsharSutra.
Result:
In the study the effect of Guggulu Chitraka KsharSutra was found better in pain, itching, pus discharge, tenderness and burning sensation and the rate of Unit Cutting Time was slightly higher as Snuhi Apamarga KsharSutra.
Conclusion:
Though U.C.T of Guggulu Chitrak Kshara Sutra is slightly higher than Snuhi Apamarga Kshar Sutra, but in assessment parameter Guggulu Chitrak Kshar Sutra has been shown significant result. With guggulu chitrak ksharsutra post ligation complications like hypertrophied scar etc are not seen and this is easily available and cost effective.
doi:10.4103/0257-7941.123848
PMCID: PMC4147504
4.  A comparative study of Kaishora Guggulu and Amrita Guggulu in the management of Utthana Vatarakta 
Ayu  2010;31(4):410-416.
Vatarakta is the major example of Vata vyadhi, caused due to avarana pathology. The scenario of Utthana Vatarakta occurred owing to the margavarana pathology, which can very well be correlated with atherosclerotic peripheral arterial disease. The literature enlists a number of Guggulu prayogas in the management of Vatarakta. An additional cavernous revise was indispensable to bring out the precise outcome of these products. Keeping these visions in mind, the particular comparative study was performed with Kaishora guggulu and Amrita guggulu, which are explained in the same context. This is a single-blind comparative clinical study with a pre-test and post-test design, wherein a minimum of 30 patients of either sex, suffering from Utthana Vatarakta, in an age limit of 16 to 70 years, were selected and randomly categorized into two groups. The 15 patients of group A were treated with oral administration of Tab Kaishora guggulu 1 g thrice a day and the group B patients with Tab Amrita guggulu of the same dose pattern with anupana of lukewarm water. The therapeutic effect of the treatment was assessed in both the groups based on specific subjective and objective parameters. The results obtained were analyzed statistically in both the groups and the comparative effect was assessed using the unpaired “t” -test. In the present study, 80% of the patients from both the groups had madhumeha (Diabetes mellitus), shonita mada (Hypertension) or both. Fifty percent of the patients in group A and nearly 60% of the patients in group B, suffering from Utthana Vatarakta, had the habit of smoking.In both the groups, a statistically significant improvement was observed in all the criteria of assessment. The outcome of the study revealed an identical therapeutic efficacy of Kaishora guggulu and Amrita guggulu in Utthana Vatarakta. The use of Kaishora guggulu or Amrita guggulu as shamana Aushadhas was a perfect selection in the management of rakta margavaranajanya Utthana Vatarakta.
doi:10.4103/0974-8520.82027
PMCID: PMC3202258  PMID: 22048531
Utthana Vatarakta; Margavarana; Raktavahasrotas; Atherosclerosis; Peripheral Vascular Diseases
5.  Cultivation and Conservation of Guggulu (Commiphora mukul) 
Ancient Science of Life  2009;29(1):22-25.
Guggulu (Commiphora mukul) is about 2-3.5 mt heighted plant of Burceraceae family. The plant grows wild in the arid, rocky tracts, also in low rainy and hot areas. The part used in medicinal preparation is resin, collected by tapping the barks. Guggulu deserves high values in Ayurvedic medicines. Guggulu is Rasayana, Vatakaphaghna, and used in various diseases. Due to high values and excessive demands, improper methods of collection, uncontrolled forest destruction and poor knowledge of cultivation; number of plants highly decreased. Now it categorized as threatened plant. Hence cultivation and conservation of this plant is necessary. Guggulu can be propagated by seed and vegetative method. Germination through seed is very poor. Vegetative propagation through stem cutting is most common and successful method. Farming care is also necessary f or proper growth. Conservation can be effected by knowledge of collection methods and awareness.
PMCID: PMC3336300  PMID: 22557340
Commiphora mukul; tapping; cultivation; Germination; Vegetative propagation; Conservation
6.  A comparative study of Rasona Rasnadi Ghanavati and Simhanada Guggulu on Amavata with special reference to Rheumatoid arthritis 
Ayu  2011;32(1):46-54.
The present study was aimed to assess the clinical effectiveness of Rasona Rasnadi Ghanavati and Simhanada Guggulu along with Rasona Rasnadi Lepa in Amavata, and to compare the effect of these two therapies in the treatment. Total 101 patients of Amavata were registered for the present study and were randomly divided into two groups. In group A- Rasona Rasnadi Ghanavati 2 Vati thrice/day was given for 3 months, while in group B- Simhanada Guggulu 2 Vati thrice a day for 3 months was adminstered. Along with this, Rasona Rasnadi Lepa was applied locally over affected joints twice daily in both groups. The effects of therapy in both groups were assessed by a specially prepared proforma. The results of the study showed that both the groups showed significant relief in symptoms; however, compared to Simhanada Guggulu, Rasona Rasnadi Ghanavati showed better result in the management of Amavata. Simhanada Guggulu or Rasona Rasnadi Ghanavati along with Rasona Rasnadi Lepa can be used as an effective ayurvedic intervention in the treatment for rheumatoid arthritis.
doi:10.4103/0974-8520.85724
PMCID: PMC3215416  PMID: 22131757
Ama; Amavata; Rasona Rasnadi Ghanavati; Rheumatoid arthritis; Simhanada Guggulu; Vata
7.  Development and Characterization of Enteric-Coated Immediate-Release Pellets of Aceclofenac by Extrusion/Spheronization Technique Using κ-Carrageenan as a Pelletizing Agent 
AAPS PharmSciTech  2010;11(1):336-343.
In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion–spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like β-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% κ-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of κ-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.
doi:10.1208/s12249-010-9389-9
PMCID: PMC2850460  PMID: 20195805
aceclofenac; enteric-coated; κ-carrageenan; pellets
8.  PA01.70. A clinical study on the efficacy of Jalaukawacharana in the management of janu sandhigata vata w.s.r. To osteoarthritis of knee joint 
Ancient Science of Life  2012;32(Suppl 1):S120.
Purpose:
The sandhigata vata described in Ayurveda causes the symptomatology such as shula, sotha, stambhana, sparsha asahyata, sputana, akunchana prasarana vedana etc. whereas the osteoarthritis described in modern science can be correlated with sandhigata vata because it also produces the features such as inflammation, pain, stiffness, limited movements and deformity in severe cases. Osteoarthritis is the 2nd most common illness with 22 29% of prevalence in global population. Presently available modern medication is causing many side and toxic effects which sometimes may need hospitalization also. Hence it requires the need to find such a therapy which gives better relief without any side or toxic effects and also natural, cost effective and easily available. Hence the non surgical biological therapeutic means such jalaukawacharana was selected.
Method:
Total of 20 patients were selected on the basis of selection criteria (inclusion and exclusion criteria) and then they are grouped into two i.e. 10 each in Jalukawacharana and Yogaraja guggulu group. The jalukawacharana was done with 7 day interval for about 6 sittings in 1st group where as in 2nd group yogaraja guggulu 125mg thrice a day was given for 6 weeks. For assessment, the Koos was taken as subjective and range of motion was taken as objective parameter for proper assessment and they are subjected for statistical validity.
Result:
After analyzing, the jalukawacharana shown significant and remarkable result in comparison with Yogaraja guguulu. The symptomatology was reduced to great extent and range of motion is also improved a lot by jalukawacharana than with yogaraja guggulu.
Conclusion:
The janu sandhi gata vata can correlate or compared with osteoarthritis of knee joint. The non surgical, biological therapeutic means i.e. jalukawacharana shown good result in treating with janu sandhigata vata i.e. osteoarthritis of knee joint in comparison with standard group i.e. yogaraja guggulu.
PMCID: PMC3800875
9.  Development of a chewable tablet from Dugdhāmalakyādi Yoga: An Ayurvedic preparation 
Ancient Science of Life  2012;32(1):34-37.
Background:
Āmalaki (Embelica officinalis Gaertn.) is one of the most celebrated herbs in the Indian system of traditional medicine. It is one of the best Rasāyana-s (health promoting) drug. In Dugdhāmalakyādi yoga, Āmalaki (Embelica officinalis Gaertn.) powder is administered along with milk in case of svarabhaṅga (hoarseness of voice). Here an attempt is made to convert this formulation into chewable tablet without altering its property to improve its palatability, shelf life and fixation of proper therapeutic dose.
Methodology:
Chewable tablets were prepared by wet granulation method. Here, Āmalaki powder was prepared initially and it was mixed with additives and preservatives. Granules were prepared from this mixture by adding binding agent, finally compressed in to tablets.
Results and Conclusion:
The physico-chemical analysis of Āmalaki standard are: Foreign Matter-Nil, Acid insoluble Ash-0.51%w/w, Water soluble Ash-2.01% w/w, Alcoholic Extractives-44.48%, Aqueous Extractives 67.52%, pH-3.1, Moisture content-8.19%. Quality control test for chewable tablet was carried out and found satisfactory with general characteristics of tablet viz. hardness 1.8, disintegration time 15-20 min, friability 0.5%, weight variation +/- 3%. The TLC of Āmalaki powder showed 3 spots with Rf value 0.14, 0.4, and 0.73 and the chewable tablets showed 2 spots with Rf value 0.31 and 0.89 under 254 nm. The adaptation of modern techniques or methods to convert the Ayurvedic formulations without altering its therapeutic property is necessary to made them suitable for the present trends of newer drug delivery dosage forms.
doi:10.4103/0257-7941.113802
PMCID: PMC3733205  PMID: 23929992
Embelica officinalis Gaertn; chewable tablets; Dugdhāmalakyādi yoga
10.  Response Surface Methodology to Optimize Novel Fast Disintegrating Tablets Using β Cyclodextrin as Diluent 
AAPS PharmSciTech  2010;11(4):1627-1635.
The objective of this work was to apply response surface approach to investigate main and interaction effects of formulation parameters in optimizing novel fast disintegrating tablet formulation using β cyclodextrin as a diluent. The variables studied were diluent (β cyclodextrin, X1), superdisintegrant (Croscarmellose sodium, X2), and direct compression aid (Spray dried lactose, X3). Tablets were prepared by direct compression method on B2 rotary tablet press using flat plain-face punches and characterized for weight variation, thickness, disintegration time (Y1), and hardness (Y2). Disintegration time was strongly affected by quadratic terms of β cyclodextrin, croscarmellose sodium, and spray-dried lactose. The positive value of regression coefficient for β cyclodextrin suggested that hardness increased with increased amount of β cyclodextrin. In general, disintegration of tablets has been reported to slow down with increase in hardness. However in the present study, higher concentration of β cyclodextrin was found to improve tablet hardness without increasing the disintegration time. Thus, β cyclodextrin is proposed as a suitable diluent to achieve fast disintegrating tablets with sufficient hardness. Good correlation between the predicted values and experimental data of the optimized formulation validated prognostic ability of response surface methodology in optimizing fast disintegrating tablets using β cyclodextrin as a diluent.
doi:10.1208/s12249-010-9541-6
PMCID: PMC3011066  PMID: 21086083
β cyclodextrin; central composite design; fast disintegrating tablets; granisetron hydrochloride; response surface
11.  PA03.19. Clinical study on the effect of Moorchita Tila Taila Shamana Sneha and Navaka Guggulu in Hyperlipidemia – A comparative study 
Ancient Science of Life  2013;32(Suppl 2):S88.
Purpose:
Hyperlipidemia is a disorder which is identified as a potential risk factor for multitudes of diseases like cardiovascular diseases, metabolic syndrome and even hypertension. Hyperlipidemia is term used to denote raised serum levels of cholesterol or triglycerides or both. Though, there is no precise terminology for Hyperlipidemia mentioned in the Ayurvedic classics, A detailed study of Hyperlipidemia reveals its similarity to Asthayi Medo Dhatu Vriddhi on the basis of its Pathophysiology.
Method:
For Group A Moorchita Tila Taila 15ml twice daily as Shamana Sneha with Ushna jala for 30 days. For Group B Navaka Guggulu in Tablet form 500mg, 1 tab thrice daily for 30 days.
Result:
Both the groups A and B showed reduction in serum Total Cholesterol, Triglycerides, LDL–C and VLDL–C and Group A showed slight increase in HDL levels.
Conclusion:
Shamananga snehapana can be safely carried out in patients of Hyperlipidemia. Comparing both the groups, Group A treated with Moorchita Tila Taila Shamana Sneha showed better results in reducing serum lipid values than Group B treated with Navaka Guggulu
doi:10.4103/0257-7941.123916
PMCID: PMC4147563
12.  Clinical effect of Nirgundi Patra pinda sweda and Ashwagandhadi Guggulu Yoga in the management of Sandhigata Vata (Osteoarthritis) 
Ayu  2011;32(2):207-212.
Sandhigata Vata is one among the 80 Nanatmaja Vata Vyadhies. Sandhigata Vata and Osteoarthritis have common symptoms, and hence, both are considered as similar entities by a majority of Ayurvedic scholars and same has been adopted here. Osteoarthritis is the most common joint disease among human beings today. In this study, a total of 116 patients were registered, out of them 101 patients had completed the full course of treatment, while 15 patients left against medical advice. The 101 patients of Sandhigata Vata were treated in two groups. Group A: In this group 50 patients of Sandhigata Vata were treated with Nirgundi Patra pinda sweda for 21 days and Ashwagandhadi Guggulu Yoga3 g/day for 45 days was given orally. Group B: In this group 51 patients of Sandhigata Vata were treated with only Ashwagandhadi Guggulu Yoga 3 g/day for 45 days. To assess the effect of the therapy objectively, all the signs and symptoms of Sandhigata Vata were given a score, depending upon their severity. Also functional tests like walking time, climbing stairs, and joint movement, were measured as a criteria for assessment. Both the groups showed good results, but Group B showed better results in comparison to group A
doi:10.4103/0974-8520.92588
PMCID: PMC3296342  PMID: 22408304
Ashwagandhadi Guggulu Yoga; Nirgundi Patrapinda Sweda; Osteoarthritis; Sandhigata Vata
13.  The suitability of disintegrating force kinetics for studying the effect of manufacturing parameters on spironolactone tablet properties 
AAPS PharmSciTech  2003;4(2):50-56.
The aim of this paper was to study the effect of the granulate properties and tablet compression force on disintegrating force behavior in order to investigate the capability of the disintegrating force to characterize tablets that have the same composition but were manufactured in different conditions. Several tablets containing spironolactone in the external or internal granulated mixture of calcium carbonate and maize starch differing in particle size distribution, were prepared at 3 compression levels. The force developed by tablets during water uptake and disintegration was measured and plotted versus time. The curves obtained were analyzed by the Weibull equation in order to calculate the parameters characterizing the tablet disintegration kinetics. The disintegrating force time parameter, the maximum force developed, and the area under the curve were determined. In general, the reduction of time parameter value and/or the increase in maximum force developed corresponded to an acceleration in tablet disintegration. In addition, the area under the force curve increased in stronger tablets, monitoring in a sensitive way the tablet structural changes introduced by compression force. The results showed that the disintegrating force measurement can detect small changes in the structure of the tablet that cannot be discriminated by pharmacopoeia tests. The effect of manufacturing, in particular compression force, on tablet properties was quantified by the parameters of disintegrating force kinetics.
doi:10.1208/pt040217
PMCID: PMC2750595  PMID: 12916899
disintegrating force; spironolactone; tablet; granulation; compression force
14.  Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion 
AAPS PharmSciTech  2006;7(2):E167-E175.
The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 32 randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.
doi:10.1208/pt070255
PMCID: PMC2750282  PMID: 16796372
rofecoxib; polyvinyl pyrrolidone K30; solid dispersion; solvent method; mouth dissolve tablets; factorial design
15.  Preparation and evaluation of sublingual tablets of zolmitriptan 
Aim:
Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan.
Materials and Methods:
Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline.
Results:
The in-vitro disintegration time of the optimized formulation (D5) was 9 ± 2 s and all formulations showed 100% of dissolution within 6 ± 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline.
Conclusion:
The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action.
doi:10.4103/2230-973X.127737
PMCID: PMC3944614  PMID: 24678459
Ex-vivo permeation; natural super disintegrants; permeation enhancers; sublingual tablets; zolmitriptan
16.  Pills, Thrills and Bellyaches: Case Studies of Prescription Pill Use and Misuse among Marijuana/Blunt Smoking Middle Class Young Women 
Contemporary drug problems  2007;34(1):53-101.
Recent survey research has documented important increases during the 2000s in the misuse and abuse of several prescription drugs (Vicodin, Percocet, Codeine, Dilaudid, Xanax, Klonopin, Valium, Ativan, Adderall, Ritalin, among others). This article focuses upon the patterns of pill use and misuse among young women who are middle-class white and college-educated, and they are also experienced marijuana users who report recreational consumption of other illegal drugs. The ethnographic data provides insights about various ways and reasons that such prescription pill misuse occurs among 12 college-educated, (upper) middle-class, white/Asian women in their 20s who were involved in a major ethnographic study of marijuana and blunts. Three patterns of pill use were observed: recreational; quasi-medical; and legal medical; shifts among these patterns of pill use was common. Few reported that their pill use interfered with their conventional jobs and lifestyles; they concealed such use from their employers and coworkers, and from non-using friends and family members. None reported contacts with police nor seeking treatment specifically for their pill misuse. Many reported misusing prescription pills in conjunction with illegal drugs (marijuana, cocaine, ecstasy) and alcohol. Pills were used as a way to enhance the euphoric effects of other drugs, as well as a way to avoid the negative side effects of illegal drugs. Some reported pill use as a means for reducing expenditures (and use of) alcohol and cocaine. The implications suggest a hidden subpopulation of prescription pill misusers among regular users of marijuana and other illegal drugs. Future research should include users and misusers of various pills to better understand how prescriptions pills interact with illegal drug use patterns.
PMCID: PMC2600420  PMID: 19081798
17.  Fast dissolving strips: A novel approach for the delivery of verapamil 
Objective:
Fast dissolving drug delivery system offers a solution for those patients having difficulty in swallowing tablets/capsules etc. Verapamil is a calcium channel blocker used as an antianginal, antiarrhythmic, and antihypertensive agent with extensive first pass metabolism which results in less bioavailability. This work investigated the possibility of developing verapamil fast dissolving strips allowing fast, reproducible drug dissolution in the oral cavity; thus bypassing first pass metabolism.
Materials and methods:
The fast dissolving strips were prepared by solvent casting technique with the help of HPMC E6 and maltodextrin. The strips were evaluated for drug content uniformity, film thickness, folding endurance, in vitro disintegration time, in vitro dissolution studies, surface pH study, and palatability study.
Results:
Official criteria for evaluation parameters were fulfilled by all formulations. Disintegration time showed by formulations was found to be in range of 20.4–28.6 sec. Based on the evaluation parameters, the formulation containing 2% HPMC E6 and 3.5% maltodextrin showed optimum performance against other formulations.
Conclusion:
It was concluded that the fast dissolving strips of verapamil can be made by solvent casting technique with enhanced dissolution rate, taste masking, and hence better patient compliance and effective therapy
doi:10.4103/0975-7406.72133
PMCID: PMC2996061  PMID: 21180465
Fast dissolving strips; HPMC E6; maltodextrin; verapamil
18.  PA01.81. Impact of globalisation on health w.s.r. metabolic syndrome and its ayurvedic management) 
Ancient Science of Life  2012;32(Suppl 1):S131.
Purpose:
According to WHO report 2002,Cardiovacular diseases (CVD) will be the largest cause of death and disability in India by 2012. Metabolic Syndrome (MetS), a constellation of dyslipidemia, elevated blood glucose, hypertension and obesity is emerging as the most common risk factor for CVD. The rising prevalence of individual components of Metabolic Syndrome is mainly attributed to globalisation which has made available cheap, unhealthy food on the main menu & also brought with it sedentary lifestyle. It is a need of time to pay due consideration on the problem and search for alternative medicine. So the aim of the study is: 1. To study the impact of globalisation on health w.s.r Metabolic Syndrome. 2. To assess the clinical efficacy of Panchakarma in its management.
Method:
For the study large-scale survey, other documented data and published articles were studied. For clinical contrieve 20 patients were registered and were given Virechana Karma followed by administration of Shuddha Guggulu as palliative measure.
Result:
The results show that globalisation has a great impact on all the components of Metabolic Syndrome. However on management with Panchakarma (Virechana Karma) followed by Shuddha Guggulu encouraging results were found. The overall effect of therapy was found to be 82.5%.
Conclusion:
There is a high prevalence of metabolic syndrome in India and it is a need of time to consider alternative treatment for its management alongwith change in lifestyle to reduce the risk of cardiovascular disease.
PMCID: PMC3800887
19.  THE FATE OF THE GIANT CELLS IN HEALING TUBERCULOUS TISSUE, AS OBSERVED IN A CASE OF HEALING TUBERCULOUS MENINGITIS 
From the foregoing description of the histological changes in the leptomeninx it is quite evident that we are dealing with a chronic, stationary, healing form of tuberculous inflammation. This statement is substantiated, in the first place, by the clinical history. The only reasonable interpretation of the symptoms would establish the duration of the process as four months. The imaginable contingency that there existed first a meningeal syphilitic lesion that was dispersed by the iodide of potassium only to be followed by a tuberculous infection is so remote and unlikely that it need not be discussed. At all events the tuberculous leptomeningitis, which presented a typical distribution, began insidiously, existed at times in a latent condition, and pursued a very anomalous course, marked by a relative mildness of all the symptoms, and thus it came about that when an apparent or real improvement followed the administration of iodide of potassium able observers were induced to make an erroneous diagnosis. Death occurred as a result of an intercurrent infection. The long duration of the process is also shown, anatomically, by the thick layer of firm, translucent and gelatinous material that matted together the structures at the base, and also by the evident adhesions between the pia and the brain. The histological examination furnishes proof positive of the correctness of the conclusion in regard to the peculiar character of this process because it shows: (1) That the tuberculous proliferation is uniform in development and has reached nearly the same stage of evolution throughout the entire extent of the leptomeninx involved; it is not a process that has advanced by exacerbations and irregular extensions; the lesions are, generally speaking, of nearly the same age everywhere and must have begun at about the same time. (2) That only a very limited degree of caseous degeneration is present, pointing to an early arrest of the activity of the tubercle bacillus or to a very decided diminution or attenuation of its virulence. (3) That the subendothelial intimal proliferations of epithelioid cells, so generally found in acute tuberculous leptomeningitis,* have in this case become more or less completely changed into distinct fibrous tissue in which but very slight, if any, direct evidence of its tuberculous origin can be found. It is only by recognizing that the chronic endarteritis is most marked in correspondence with the most advanced adventitial tuberculous changes, and by finding an imperfect, much altered giant cell in one district of intimal thickening, that we were able to establish the direct kinship of the endovascular changes with those of the pia in general. (4) That acute inflammatory changes, in the form of emigration of polymorphonuclear leucocytes and of fibrinous exudation, are entirely absent in all parts of the district involved. The presence of a turbid serous fluid is of course not at all inconsistent with the view that the anatomical changes are of long duration. (5) That the granulation tissue present is, in general, undergoing fibrillation and contains a rich supply of enabryonal capillary vessels as well as of larger blood-vessels of evidently new formation. The absence of any considerable extent of polymorphonuclear leucocytic infiltration in this tissue has already been referred to. The cells in the granulation tissue correspond to the cells of embryonal or formative connective tissue. Vacuolation is rarely present. (6) That the unusually large number of giant cells present are remarkably free from evidences of necrosis and degeneration of the character ordinarily observed in tuberculous proliferations, that they do not contain in demonstrable form tubercle bacilli, and that the majority of the giant cells seem to be separating into individual cells and smaller masses often with, but sometimes also without, evidences of nuclear disintegration. The possibility that these phenomena may signify fusion instead of the sundering of cells will be discussed below. For these reasons there can be no doubt that the general claim that we are dealing with an instance of chronic, healing tuberculous meningitis must be regarded as established beyond dispute. The growth of tubercle bacilli in the glycerine-agar tubes, inoculated with the fluid from the pial meshes, and the demonstration of tubercle bacilli, though in very small numbers, between the cells of the embryonal tissue, furnish the positive evidence that we are actually dealing with a tuberculous process due to living and not to dead bacilli. The degree of virulence of the cultures of tubercle bacilli was, unfortunately perhaps, not studied. The presence of living tubercle bacilli in a tissue free from active and acute changes characteristic of tuberculosis demonstrates that, whatever the actual degree of virulence of the bacilli may have been, the tissue in which they were found was at this time relatively immune from their action. The manner in which this immunity was produced, and in which the process of healing was initiated, need not be discussed at this time any further than to again direct attention to the fact that the bacilli lost their virulency as regards the cells in this leptomeninx before these cells underwent any marked degree of degeneration. The cells of the tuberculous proliferations survived the further action of the bacilli whose original effect it was to initiate cell accumulation or proliferation; the cells also retained sufficient vitality to develop, in some instances at any rate, into formative cells according as their origin would dictate, e. g. into fibroblasts. That fibroblasts are formed only by embryonal connective tissue cells, and not by wandering cells, such as the large mononuclear leucocytes, we are well aware, is possibly still a disputable assumption, and we do not consider it pertinent to discuss the question any further in connection with this study, but would only emphasize the point that some of the cells of tuberculous proliferations may, under favorable circumstances, become formative cells, and, furthermore, that the amount of formative tissue produced may be far in excess of what is actually needed for purposes of repair only. Surely the appearances here noted indicate that the bacillus of tuberculosis has the power to stimulate fixed cells to multiply, unless one assumes that all, or almost all, the formative cells here seen are derived from wandering cells attracted by the presence of the bacillus and its products. As to the ultimate fate of the formative and other cells in this healing tuberculous tissue no final statements can be made. It must be remembered that it is only one stage in the process of healing that is dealt with. The well marked evidences of fibrillation, the quite extensive formation of new vessels, the absence of evidences of degenerative changes in the uninuclear cells, all point to the production of new fibrous tissue as sure to occur, but it seems quite probable that occasional epithelioid cells may undergo or have undergone dropsical or other forms of degeneration, although it is certainly apparent that so far as the small cells are concerned the involution of the tuberculous tissue is not occurring through disintegration. Perhaps the most interesting feature in this case is the opportunity it affords to study the changes in the giant cells of healing, non-degenerated tuberculous tissue. In the first place, the large number of giant cells is quite remarkable. The general characters of the tissue in which they are found recall the fact that giant cells are regarded as quite constant elements in chronic mild tuberculosis; often the giant cells are the only cells that contain bacilli (Koch). In this instance the giant cells do not contain bacilli that are demonstrable by the usual methods; neither do they contain bodies that can be definitely interpreted as degenerate forms of bacilli such as those found by Metchnikoff, Stchastny, Weicker, and others, in the giant cells of Spermophilus guttatus, in avian and in human tuberculosis. Metchnikoff states, however, that he knows of the occurrence of such degenerate forms only in the Spermophilus guttatus under the circumstances mentioned, and in the rabbit and guinea-pig in mammalian tuberculosis, but not in man; consequently, the manner in which the giant cells rid themselves of the bacilli undoubtedly present in their interior at some time during their existence, must as yet remain without any explanation. In the description of the histological changes the various appearances presented by the giant cells are described somewhat minutely. The essential observations made concern, in my opinion, the further fate of giant cells which are still found to persist in healing nondegenerated tuberculous tissue. It was, I believe, quite conclusively shown that the consecutive changes appear to consist in the breaking up of the nuclei, the removal of the detritus by phagocytes, and the formation of a few apparently viable uninuclear cells in the case of more degenerated, exhausted giant cells, while other, and, as it would seem, better preserved or younger giant cells, separate into a number of individual, uninuclear cells with but little or no nuclear disintegration. Objection might be raised to this interpretation of the appearances in the giant cells. While no one could very well dispute the view that part of the giant cells are undergoing retrogressive and absorptive changes with the production of some viable cells, a question might well be raised concerning the nature of the process taking place in those giant cells that have been spoken of as splitting up or dividing into uninuclear cells and smaller multinucleated masses without much evidence of nuclear disintegration. It might be claimed that the process is one of fusion of many cells to form giant cells, and not one of division of fully formed giant cells into small cells. But a broad view of the processes described speaks against fusion. In the first place we are not dealing with a stage of tuberculous proliferation (Baumgarten), or cell accumulation (Metchnikoff), in which one would look for the production of giant cells, no matter which view concerning the histogenesis of tubercle be assumed as the correct one, because it has been demonstrated that, from whichever point of view the lesions are examined, the same positive conclusion that they are in the process of healing is reached; there is, therefore, no occasion for the formation of new giant cells in such wide-spread degree throughout the district involved. It might he claimed that the cells became arrested and, as it were, fixed in the act of fusion which was taking place in the early stage of the meningitis, but it would be difficult to understand the nature of the stimulus that could hold the cells together in such a peculiar manner for such a long time. It must be remembered that bacilli or bacillary detritus could not be found among the incomplete or in the complete giant cells. In the second place the difference between the cells that are undergoing disintegration and those regarded as dividing is essentially, to a certain extent at any rate, one of degree, because in the first instance there is not much, if any, doubt but that viable smaller cells are also formed, and in the second instance some, though often very slight, evidence of nuclear fragmentation is nearly always present; it would also be correct to infer that in advanced subdivision of a giant cell much, and perhaps all, of the nuclear detritus produced might have been removed up to the last trace; finally, the two extremes of these changes in the giant cells are connected by transition stages passing by gradation from the one to the other. Hence it is justifiable to conclude, for the time being, that in healing non-degenerated tuberculous tissue, the multinucleated giant cells may in part disintegrate and undergo absorption, in part form viable small cells; that both these changes may, and usually do, affect the same cell, but that in one class of cells—presumably the older or the more exhausted—the retrogressive process is predominant, while in a second class of cells—presumably the young and vigorous—the progressive changes are the more marked. In this connection it may be pointed out that while there cannot very well be any question but that we are dealing only with dividing and not coalescing cells, yet if this conclusion should be disputed and found incorrect, then the only remaining alternative would be to infer that this tissue furnished a unique and striking example of the formation of plasmodial masses by fusion in human tuberculosis, a conclusion to which many pathologists would refuse to subscribe, if for no other reason than because it is not in accordance with the almost universally accepted teachings of Baumgarten and Weigert in regard to the mode of formation of the giant cells in tuberculosis. Believing as I do that the giant cells under consideration are in the act of division and not at all of fusion, there remain to be discussed some of the histological and other features presented by the dividing cells. Many of the giant cells, perhaps the majority, contain larger and smaller vacuoles in the protoplasm. The exact significance of this vacuolation is not always clear. When the vacuolation accompanies an evident solution of the nucleus (karyolysis), there cannot be any doubt but that we are in the presence of a distinctly retrogressive process. Vacuoles are also most numerous in the giant cells that present other evidences of degeneration, such as coarseness of the granules in the protoplasm and extensive nuclear disintegration, but they occur as well around nuclei that stain deeply, around cells that seem to be separating from the giant cell, and even about nuclei that present mitoses. The formation of vacuoles seems to be responsible, to a certain extent at any rate, for the diminution in the volume of disintegrating and dividing giant cells, as shown by the clear spaces that form about them; these spaces are too large and occur too uniformly to be attributed solely to artificial shrinking produced by the hardening in alcohol. Further undoubted evidence of retrogression in certain giant cells is the occurrence of nuclear disintegration, or karyorhexis, which sets free larger and smaller chromatin masses that are recognized in the giant cell as well as in the interior of the phagocytes usually found around such cells. Almost all the polymorphonuclear leucocytes found in this tissue are met with around giant cells with broken-up nuclei. In many nuclei of disintegrating giant cells can be noted appearances that correspond well to certain stages in the complicated karyorhexis observed in anæmic necrosis by Schmaus and Albrecht; some of the nuclei with budding processes correspond particularly well with those in certain of their drawings; the interior of giant cells of tuberculous tissue may, it would seem, present conditions favorable to the development of this series of postnecrotic nuclear change. Vacuolation, karyolysis and karyorhexis are the essential steps that lead to destruction of the whole or parts of some of the giant cells; associated with these processes there is usually observed a splitting up of the body of the giant cell into irregular fragments with as well as without nuclei; and, as described, more or less phagocytosis of the resulting remnants of various kinds is seen. But evident degenerative and necrotic processes in a giant cell may be associated with progressive changes. While some nuclei undergo vacuolation or break up, others seem to become richer in chromatin and to stain more deeply at the same time that they seem to acquire cell bodies quite distinct from the protoplasm of the giant cells: this hyperchromatosis does not, therefore, seem to be a stage in karyorhexis. A very few but undoubted karyokinetic figures were found, together with evidences of division of the cell body formed in the giant cell protoplasm. Precisely similar changes are described by Klebs in healing pulmonary tuberculosis of the guinea-pig; the nuclei of the giant cells became rich in chromatin and karyokinetic figures occurred. Krückmann among others has found occasional mitoses in giant cells around foreign bodies, as well as elsewhere, but it would seem that such mitoses have always been interpreted as indicating the probable mode of formation of the giant cells rather than of their involution. The question of mitosis in existing multinucleated cells has recently been studied by Krompecher, who concludes that the individual nuclei of such cells may undoubtedly divide by mitosis, either simultaneously or at separate times. Division by amitosis can also occur, but mitosis is the only progressive form of division, amitosis being a retrogressive, disintegrating process that must be looked upon as an evidence of degeneration of the nucleus. Ziegler states that in division of giant cells whose nuclei have multiplied by mitosis it may happen that the separating cell remains enclosed in the protoplasm of the mother cell. A singular phase in the involution of the giant cells in this pia is to be found in the existence of progressive changes side by side with nuclear necrosis and with degeneration; this finding indicates that giant cells may contain many independent elements which, though apparently fused into one large cell, may preserve their individuality so that while some nuclei die, others proliferate and perhaps feed on the remnants of their dead brethren and form new, viable small cells. The nuclei in giant cells may be looked upon as representing independent centres, capable at times of existing even though the cell protoplasm is disintegrated. Many of the giant cells separate into individual cells, unaccompanied or unassociated with much evidence of necrosis. These cells may be regarded as the more vigorous forms. Here also are observed occasional mitoses—but on the whole extremely few—and very constantly an evident increase in the amount of chromatin in the nuclei of the new cells as compared with the amount ordinarily found in the nuclei of giant cells. These deductions concerning the persistence of the vitality of some of the nuclei, even in the presence of molecular and morphological changes in the cytoplasm and in other nuclei of the giant cell that lead to disintegration, are not entirely without the support of previous observations on cells, which, although made under different conditions, are nevertheless, it would seem, applicable to cells in general. Thus the brilliant investigations of Loeb upon the effects of various unfavorable surroundings, such as absence of oxygen or reduction of the amount of water, upon the cleavage of eggs of many kinds, show that the conditions which arrest development are qualitatively alike for nucleus and protoplasm, but quantitatively less for the protoplasm; when the irritability of the protoplasm is suspended the nucleus may segment without segmentation of the protoplasm, but upon re-establishment of favorable conditions the protoplasm may divide into about as many spheres as there are nuclei preformed—the nucleus persists, preserves the irritability of the cell and stimulates the protoplasm to segmentation. From the appearances of the giant cells here described it would seem, then, that some nuclei are able to maintain their vitality longer than others in the same cell, and under certain conditions to stimulate parts of the protoplasm to segment; in other cells all the nuclei have, as a rule, preserved their irritability. The groups of cells formed by the dividing of the giant cells can be traced by studying the process at the different stages in the different parts of the tissue. They assume an oval or spindle-shaped form, becoming more and more like the formative and endothelioid cells of young connective tissue, but their ultimate fate cannot be determined because it concerns essentially only one limited period in the involution of the tissue. It may be said with reasonable certainty, however, that the new cells do not form blood-vessels, but as regards their forming lymph-vessels nothing definite can be concluded. It would not be safe to draw any definite conclusions, from the appearances described, with regard to the origin and the mode of formation of the giant cells. The resulting small cells in general resemble very much endothelial and formative cells, but some of them are, at certain stages at any rate, not unlike large mononuclear leucocytes; their final fully developed or mature condition being unknown, no positive inference can be drawn as to their pre-giant-cell origin. The evidence points to the fact that the most probable origin of the giant cells, as indicated by their form and the apparent future career of their descendants, would be the fixed mesoblastic cells of the pia. In regard to the mode of formation of the giant cells it is quite clear that it must involve some process which is not incompatible with the viability of the small cells which may spring from the giant cells. Whether this would speak more in favor of formation by fusion than by karyokinesis of a single cell without division of the cell body cannot be well determined, and as long as authors are not agreed upon the question of the production of living, procreative cells by amitosis (direct segmentation, direct and indirect fragmentation) it would not be profitable to discuss the compatibility or incompatibility of the views of those investigators who trace the origin of giant cells to amitotic division, with the progressive changes that giant cells have been shown to be capable of. The fact that giant cells in tuberculous tissue, under certain conditions, undergo progressive changes and separate into small, living cells proves that they are not, as claimed by Baumgarten, Weigert and others, necrobiotic elements that are doomed to destruction from their very inception. On the other hand it lends more strength, if that were necessary, to the teleological view urged by Metchnikoff that they are living, defensive cells (whatever their origin may be), formed for the distinct purpose, like plasmodial masses in general, of isolating and removing foreign, harmful bodies, in this case the tubercle bacillus, and, having accomplished their object without being destroyed or exhausted, or the cause of their formation being removed or neutralized in some way, they, or their nuclei, may retain enough irritability to form a larger or smaller number of living, small, uninuclear cells.
PMCID: PMC2117963  PMID: 19866866
20.  Effect of Ayurvedic management in 130 patients of diabetic nephropathy 
Ayu  2011;32(1):55-58.
Diabetic nephropathy is a specific form of renal disease. It is a major cause of renal insufficiency and ultimately of death. The present study has been carried out to prove the efficacy of Ayurvedic drugs in the management of diabetic nephropathy, which can be helpful in reducing the need of dialysis and avoiding or delaying renal transplantation. A total of 130 patients of this disease were treated in IPD (Group A) and OPD (Group B). Ayurvedic formulations including Gokshuradi Guggulu, Bhumyamalaki, Vasa and Shilajatvadi Vati were given to all the patients for 2 months. Group A patients were given special planned food. Results were analyzed statistically using “t” test. In group A patients, highly significant reduction was found in the values of serum creatinine, blood urea and urinary excretion of albumin. Marked improvement was found in the patients’ general physical well-being, together with reduction in symptoms, in group A patients. This shows the importance of Pathyapathya in Ayurvedic management of the disease. This management may bring some new hope to the patients of diabetic nephropathy, which usually terminates to chronic renal failure and ultimately to death. Further studies are being carried out in this regard.
doi:10.4103/0974-8520.85727
PMCID: PMC3215418  PMID: 22131758
Ayurveda; diabetic nephropathy; albuminuria
21.  Effect of the mode of incorporation on the disintegrant properties of acid modified water and white yam starches 
Acid modified starches obtained from two species of yam tubers namely white yam – Dioscorearotundata L. and water yam – D. alata L. DIAL2 have been investigated as intra- and extra-granular disintegrants in paracetamol tablet formulations. The native starches were modified by acid hydrolysis and employed as disintegrant at concentrations of 5 and 10% w/w and their disintegrant properties compared with those of corn starch BP. The tensile strength and drug release properties of the tablets, assessed using the disintegration and dissolution (t50 and t80 – time required for 50% and 80% of paracetamol to be released) times, were evaluated. The results showed that the tensile strength and the disintegration and dissolution times of the tablets decreased with increase in the concentration of the starch disintegrants. The acid modified yam starches showed better disintegrant efficiency than corn starch in the tablet formulations. Acid modification appeared to improve the disintegrant efficiency of the yam starches. Furthermore, tablets containing starches incorporated extragranularly showed faster disintegration but lower tensile strength than those containing starches incorporated intragranularly. This emphasizes the importance of the mode of incorporation of starch disintegrant.
doi:10.1016/j.jsps.2011.09.001
PMCID: PMC3745072  PMID: 23960789
Yam starch; Corn starch; Acid modification; Disintegrant properties; Tablets
22.  Injectable and Oral Contraceptive Use and Cancers of the Breast, Cervix, Ovary, and Endometrium in Black South African Women: Case–Control Study 
PLoS Medicine  2012;9(3):e1001182.
A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.
Background
Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.
Methods and Findings
We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).
Conclusions
In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Hormonal contraceptives are among the most commonly used medications. Globally, more than 210 million women currently use either hormonal contraceptive pills or injectable contraceptives. Contraceptive pills usually contain manmade versions of the female sex hormones estrogen and progesterone (the combined oral contraceptive, or “pill”); most injectable hormonal contraceptives contain only manmade progesterone preparations. Hormonal contraceptives, which prevent pregnancy by disrupting the cyclical changes in estrogen and progesterone levels that prepare the body for pregnancy, have revolutionized birth control since they first became available in the early 1960s. However, it is now known that taking the pill also influences women's risk of developing cancers of the female reproductive system. Current and recent users have an increased risk of developing breast and cervical cancer (the cervix is the structure that connects the womb to the vagina) compared to never users, although this increased risk quickly disappears when women stop taking the pill. By contrast, women who have used the pill have a reduced risk of developing ovarian cancer and cancer of the womb (endometrial cancer) compared to never users that increases with the duration of pill use and persists for many years after use ceases. These effects on reproductive system cancers are thought to occur because these cancers depend on naturally occurring sex hormones for their development and growth.
Why Was This Study Done?
Although the evidence that the pill influences the risk of developing cancers of the female reproductive system is extensive, much less is known about how injectable hormonal contraceptives affect cancer risk. In this hospital-based case–control study (a study that compares the characteristics of people with and without a specific condition), the researchers investigate the relationship between the use of oral and injectable hormonal contraceptives and cancers of the breast, cervix, ovary, and endometrium among black South African women. Injectable contraceptives have been used for longer in South Africa than elsewhere and are used more commonly than oral contraceptives among black South African women.
What Did the Researchers Do and Find?
As part of the Johannesburg Cancer Case Control Study, which recruits black patients attending Johannesburg public referral hospitals for cancer treatment, the researchers compared hormonal contraceptive use in women with breast, cervical, ovarian, or endometrial cancer with contraceptive use in women diagnosed with other cancers such as lung, colon, and rectal cancers, which are not known to be influenced by hormonal contraceptives. Among the controls, a quarter had used injectable contraceptives and a fifth had used oral contraceptives. After adjusting for other factors that might influence cancer risk such as age, smoking, and number of sexual partners, the odds ratio (OR) of breast cancer among current and recent users of oral and/or injectable contraceptives compared to never users was 1.66. That is, the risk of developing breast cancer among current and recent users of hormonal contraceptives was 1.66 times that among never users. For women using oral contraceptives exclusively or injectable contraceptives exclusively, the ORs of breast cancer were 1.57 and 1.83, respectively. There were also increases in cervical cancer risk among current and recent users of hormonal contraceptives compared to never users, but no significant increase in breast or cervical cancer risk among women who had ceased hormonal contraceptive use more than ten years previously. Finally, the use of hormonal contraceptives for more than five years reduced the risk of both ovarian and endometrial cancer.
What Do These Findings Mean?
These findings indicate that, among black women in South Africa, the use of oral or injectable hormonal contraceptives is associated with a transiently increased risk of breast and cervical cancer, and that extended use of these contraceptives is associated with a reduced risk of ovarian and endometrial cancer. Moreover, they suggest that the effects of oral versus injectable contraceptives on cancer risk do not differ substantially, although for endometrial and ovarian cancer the small number of cases exposed to injectable contraceptives limits the accuracy of the risk estimates. Other limitations of this study include the possibility that the findings may be affected by uncontrolled confounding. That is, women who used hormonal contraceptives may have shared other unidentified characteristics that affected their cancer risk. Nevertheless, these findings provide new information about the effects of oral and injectable hormonal contraceptives on cancer risk that should help women make informed decisions about their choice of contraceptive method.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001182.
The US National Cancer Institute provides information on breast cancer (including personal stories from breast cancer survivors), cervical cancer, ovarian cancer, and endometrial cancer for patients and health professionals, and a fact sheet on oral contraceptives and cancer risk (in English and Spanish)
Cancer Research UK also provides information on breast cancer, cervical cancer, ovarian cancer, and endometrial cancer and information about the birth control pill and cancer risk
Eyes on the Prize, an online support group for women who have had cancers of the female reproductive system, has personal stories; further personal stories about breast, cervical, and ovarian cancer are provided by the charity Healthtalkonline
doi:10.1371/journal.pmed.1001182
PMCID: PMC3295825  PMID: 22412354
23.  Development of Mouth Dissolving Tablets of Clozapine Using Two Different Techniques 
Mouth dissolving tablets constitute an innovative dosage form that overcomes the problems of swallowing and provides a quick onset of action. In view of enhancing bioavailability an attempt has been made to study two different methods direct compression and sublimation in formulation of mouth dissolving tablets of clozapine. Total four formulations using various superdisintegrants and subliming agents were prepared. All prepared formulations were evaluated for physico-chemical parameters. The formulations exhibited good disintegration properties with total disintegration time in the range of 25 to 35 s. Comparative evaluation of two methods showed direct compression method is a better alternative to sublimation method as its formulations rapidly disintegrate in oral cavity. In vitro cumulative percentage drug release for formulations prepared by direct compression with explotab superdisintegrants shows 99.79 while sublimation method using camphor 93.58 release in 12 min. Kinetic studies indicated that all the formulations followed first order release with diffusion mechanism.
doi:10.4103/0250-474X.44611
PMCID: PMC2792538  PMID: 20046788
Clozapine; direct compression; sublimation; mouth dissolving
24.  Preparation and Evaluation of Orally Disintegrating Tablets Containing Taste-Masked Microcapsules of Berberine Hydrochloride 
AAPS PharmSciTech  2012;14(1):29-37.
The purpose of this study was to prepare and evaluate a taste-masked berberine hydrochloride orally disintegrating tablet for enhanced patient compliance. Taste masking was performed by coating berberine hydrochloride with Eudragit E100 using a fluidized bed. It was found that microcapsules with a drug–polymer ratio of 1:0.8 masked the bitter taste obviously. The microcapsules were formulated to orally disintegrating tablets and the optimized tablets containing 6% (w/w) crospovidone XL and 15% (w/w) microcrystalline cellulose showed the fastest disintegration, within 25.5 s, and had a pleasant taste. The dissolution profiles revealed that the taste-masked orally disintegrating tablets released the drug faster than commercial tablets in the first 10 min. However, their dissolution profiles were very similar after 10 min. The prepared taste-masked tablets remained stable after 6 months of storage. The pharmacokinetics of the taste-masked and commercial tablets was evaluated in rabbits. The Cmax, Tmax, and AUC0−24 values were not significantly different from each other, suggesting that the taste-masked orally disintegrating tablets are bioequivalent to commercial tablets in rabbits. These tablets will enhance patient compliance by masking taste and improve patients’ quality of life.
doi:10.1208/s12249-012-9880-6
PMCID: PMC3581648  PMID: 23180226
berberine hydrochloride; microcapsule; orally disintegrating tablet; taste masking
25.  Development and Evaluation of Artemether Taste Masked Rapid Disintegrating Tablets with Improved Dissolution Using Solid Dispersion Technique 
AAPS PharmSciTech  2008;9(2):494-500.
The purpose of this research was to mask the intensely bitter taste of artemether (ARM) and to formulate a rapid-disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by solid dispersion with mono amino glycyrrhyzinate pentahydrate (GLY) by solvent evaporation method. To characterize and formulate taste masked rapid disintegrating tablets (RDTs) of ARM, the 1:1M solid dispersion was selected based on bitterness score. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. RDTs were evaluated for weight variation, disintegration time, hardness and friability. In vitro drug release studies were performed for RDTs at pH 1.2 and 6.8. Bitterness score was evaluated using mini-column method and compared with gustatory sensation test. FTIR spectroscopy and DSC showed no interaction while XRPD showed amorphization of ARM in GLY solid dispersion. RDTs prepared using solid dispersion, (RDT3), showed faster disintegration (within 28 s) and complete bitter taste masking of ARM. In addition, RDT3 exhibited better dissolution profile at both pH 1.2 and 6.8, than RDTs prepared from pure ARM (RDT5). Taste evaluation of RDTs in human volunteers rated tasteless with a score of 0 to RDT3 and 3 to RDT5. Mini-column revealed that RDT5 showed increase in number of persons who sensed bitterness with increased amount of ARM release while RDT3 sensed no bitterness. Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity with improved dissolution.
doi:10.1208/s12249-008-9066-4
PMCID: PMC2976961  PMID: 18431657
artemether; rapidly disintegrating tablet; solid dispersion; taste masking

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