PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2004 December; 5(4): 63–68.
Published online 2004 July 27. doi:  10.1208/pt050459
PMCID: PMC2750484

Tablet formulation containing meloxicam and β-cyclodextrin: Mechanical characterization and bioavailability evaluation

Abstract

The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1[ratio]1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving the oral bioavailablity of meloxicam.

Keywords: meloxicam, β-CD, tablet, solubility, bioavailability

Full Text

The Full Text of this article is available as a PDF (166K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Moyano JR, Ginés JM, Airas MJ, Rabasco AM. Study of the dissolution characteristics of oxazepam via complexation with β-cyclodextrin. Int J Pharm. 1995;114:95–102. doi: 10.1016/0378-5173(94)00220-Y. [Cross Ref]
2. Mukne AP, Nagarsenker MS. Triamterene-β-cyclodextrin systems: preparation, characterization and in vivo evaluation. AAPS Pharm Sci Tech. 2004;5:E19–E19. doi: 10.1208/pt050119. [PMC free article] [PubMed] [Cross Ref]
3. Nalluri BN, Chowdary KPR, Murthy KVR, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems. AAPS Pharm Sci Tech. 2003;4:E2–E2. doi: 10.1208/pt040102. [PMC free article] [PubMed] [Cross Ref]
4. Giordano F, Gazzaniga A, Bettinetti GP, Manna A. The influence of water content on the binding capacity of β-cyclodextrin. Int J Pharm. 1990;62:153–156. doi: 10.1016/0378-5173(90)90229-W. [Cross Ref]
5. Tasić LJ, Pintye-Hōdi K, Sabo-Revesz P. Evaluation of compression behavior of paracetamol tablets produced with β-cyclodextrin dispersions. Part II: Energy distribution study of tablets. Drug Dev Ind Pharm. 1997;23:1153–1158.
6. Naidu NB, Chowdary KP, Murthy KV, Satyanaryana V, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary system. J Pharm Biomed Anal. 2004;35(1):75–86. doi: 10.1016/j.jpba.2004.01.003. [PubMed] [Cross Ref]
7. Baboota S, Agarwal SP. Inclusion complexation of meloxicam with β-cyclodextrin. Indian J Pharm Sci. 2002;64(4):408–411.
8. Nath BS, Shiva Kumar HN. A 2(3) factorial studies on factors influencing meloxicam β-cyclodextrin complexation for better solubility. Indian J Pharm Sci. 2000;62(2):129–132.
9. Baboota S, Agarwal SP. Effect of cyclodextrin complexation on the oral bioavailability of meloxicam. Paper presented at the 12th International Cyclodextrin Symposium; May 16–19, 2004; Montpellier, France.
10. Struengmann A, Freudensprung B, Klokkers K inventors. Pharmaceutical compositions of meloxicam with improved solubility and bioavailability. US patent 6284269. 2001.
11. Perissutti B, Rubessa F, Moneghini M, Voinovich D. Formulation design of carbamazepin fast-release tablets prepared by melt granulation. Int J Pharm. 2003;256:53–63. doi: 10.1016/S0378-5173(03)00062-0. [PubMed] [Cross Ref]
12. Shah D, Shah Y, Rampradhan M. Development and evaluation of controlled release dilitiazem hydrochloride microparticles using cross-linked poly(vinyl alcohol) Drug Dev Ind Pharm. 1997;23:567–574. doi: 10.3109/03639049709149821. [Cross Ref]
13. Aulton ME. Pharmaceutics: The Science of Dosage Form Design. London, UK: Churchill Livingstone; 1988. Pharmaceutical Technology; pp. 600–616.
14. Martin A. Physical Pharmacy. Philadelphia, PA: Lea and Febiger; 1993. Micromertics; pp. 251–283.
15. Reddy KR, Mutalik S, Reddy S. Once-daily sustained-release matrix tablets of nicorandil: formulation and in vitro evaluation. AAPS Pharm Sci Tech. 2003;4:E61–E61. doi: 10.1208/pt040461. [PMC free article] [PubMed] [Cross Ref]
16. FDA Center for Drug Evaluation and Research.Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Form. Rockville, MD: FDA: August 1997.
17. Higuchi T, Connors A. Advances in Analytical Chemistry Instrumentation. New York, NY: Wiley Interscience; 1965. Phase-solubility techniques; pp. 117–211.
18. El-Shaboury MH. Physical properties and dissolution profiles of tablets directly compressed with β-cyclodextrin. Int J Pharm. 1990;63:95–100. doi: 10.1016/0378-5173(90)90158-Z. [Cross Ref]
19. Fenyresi E, Shirankura O, Szejtli J, Nagai T. Properties of cyclodextrin polymer as a tableting aid. Chem Pharm Bull (Tokyo) 1984;32:665–669. [PubMed]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists