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Ayurvedic texts describe many formulations for different ailments. Triphala Guggulu (TG) is reputed for treating inflammatory conditions. These formulations have been considered complementary medicine or alternative to conventional medicines across the globe. These complex polyherbal formulations need science-based approach toward manufacturing process and chemical standardization.
To evaluate TG tablets to meet modern pharmaceutical approaches and also standardization processes.
Shodhana of Guggulu was performed using Triphala Kwatha (decoction) as mentioned in ayurvedic texts. This processed material was dried using spray drying technique, blended with other herbal powders as per formula and using suitable excipients was incorporated for compressing into tablets. Excipients and their concentrations were evaluated for various micromeritic properties and the formula that met the requirements was compressed.
The angle of repose was considered fair with a range of 25–30, Carr's index at a range between 17 and 30, and Hausner ratio of 1.21:1.44, which was well within the limits as per the United States Pharmacopeia (USP) and among the three blends tested, blend Triphala Guggulu formulation-3 was found most suitable for tablets compression. Physical properties were well within the limits as per the USP and disintegration time was within 30 min.
Modern pharmaceutical processing can very well be adapted for Guggulu preparations.
Herbs and herbal medicines are preferred by people since ages, and about 80% of the global population still rely on herbs and herbal remedies for chronic ailments. Ayurveda is one of the oldest systems of medicine, which is in practice since ages. Due to globalization and increased awareness, the traditional medicine usage is increasing every year. With an increase in global demand for herbal medicine, it is now important to ensure consistency in quality of products from batch to batch. To achieve this, a contemporary approach to one of the most renowned formulations mentioned in Ayurveda Triphala Guggulu (TG) was taken up as a model. This approach will help to control the process parameters during manufacturing.[2,3,4]
Among the Guggulu preparations, TG is one of the widely used preparations. Traditional texts describe in detail about the manufacturing process for the same. However, in modern practice, to fulfill market demand, an industrial approach for the traditional manufacturing process is warranted. Furthermore, with increase in demand globally, there is an unmet challenge to meet global regulations. This underlines the need to translate this Vati preparation in modern pharmaceutical dosage forms into pharmacopeial tablet formulation. In the present study, an attempt is made to adopt TG into a tablet formulation meeting the United States Pharmacopeia (USP) requirements.
TG contains following herbs as described – Guggulu (Commiphora wightii [Arn.] Bhandari) was purchased from Gujarat Medicinal Plants Growers’ Society, and other botanical substances such as Amla (Emblica officinalis Gaertn.) fruit, Haritaki (Terminalia chebula Retz.) fruit, Vibhitaki (Terminalia bellirica [Gaertn.] Roxb.) fruit, and Pippali (Piper longum L) fruit were purchased from local market of Bengaluru, Karnataka, and were authenticated by Botanist of The Himalaya Drug Company, Bengaluru. Excipients such as tapioca native starch (B. No. 12-11-07-A; South East Asia Organic Company, Thailand); Kollidon CL (B. No. 02817168EO; BASF, India); and magnesium stearate (B. No. 125912; Amish Drugs, India) were purchased.
Shuddha Guggulu was prepared using Triphala (herbal blend in equal quantities of E. officinalis, T. chebula, and T. bellirica fruits) decoction as per the process mentioned in the Ayurvedic Formulary of India (AFI).
Preparation of Triphala Kwatha
Powdered fruit blend (5 kg) was boiled in 40 L of demineralized water for 3 h using extraction vessel with a fixed temperature ranging from 85°C to 95°C. The extract was filtered using 100 µm filter cloth. The filtrate was further used to process Guggulu.
Preparation of Shuddha Guggulu
The process involved use 5 kg of Guggulu which was tied in 100 µm muslin cloth and suspended in a SS304 vessel containing Triphala Kwatha. This vessel was then heated at a temperature between 85°C and 95°C for 3 h. Then, the material was removed, and filtrate (Shuddha Guggulu) was spray dried using spray dryer at 180°C as inlet and 110°C as outlet temperature. The dried material was collected in double-lined food grade low-density polyethylene bags, sealed, and stored in high- density polyethylene container. The dried sample was subjected to high-performance liquid chromatography analysis.
Preparation of tablets
Differential scanning calorimetry (DSC) was performed using Perkin Elmer, DSC 8000, USA. The instrument was calibrated using high purity indium metal as standard. The dynamic scans were taken in nitrogen atmosphere at a heating rate of 10°C min. The runs were made in triplicate. Compatibility between the herbal active and formulation ingredients was done by comparison of decomposition of herbal active alone and in formulation.
The spray dried powder with addition of suitable excipients helped in uniform blending. Before compression, the resultant powder was evaluated for angle of repose, bulk density (Bd), tapped density, Carr's index, and Hausner ratio.
The herbal blend, which constitutes dry extract and powdered botanicals with excipients and known quantity of demineralized water, was transferred and mixed using rapid mixer grinder. The material was dried in a fluid bed dryer at a controlled temperature of 60–70°C till the material achieved moisture of <5% and then subsequently was milled and sifted through 20# sieve. The retained material on the sieve was passed through multimill and passed through 20# again.
The three formula excipient blends were developed and evaluated for micromeritic properties; based on the results of micromeritic properties of these herbal blends, finally, blend-T3 was taken for tablet compression. Compression was performed on Cadmach 16 [Cadmach Machinery Co. Pvt. Ltd, Ahmedabad, Gujarat, India] station punching machine with rpm of 18 and pressure of 4–5 kg.
Uniformity of weight
Randomly sampled tablets (10 numbers) were weighed individually on a precision balance. The average weights were determined.
Monsanto hardness tester was used to determine tablet hardness. Ten tablets were chosen randomly and force needed for each of the tableting runs and the average values were determined.
Tablet disintegration test was performed employing disintegration tester using demineralized water at 37 ± 2°C. The time required for complete disintegration of tablets was determined by visual observation.
Friability of tablets was determined by weighing 10 tablets. These were de-dusted prior testing in an analytical balance and moved for 4 min in a friability tester with a set at a speed of 25 rpm. All loose dust was removed from the tablets. They were reweighed and the percentage friability was calculated and recorded.
Samples were prepared in methanol (20 mg/ml, for standard - 1 mg/ml) and were filtered through Whatman filter paper. Filtrates were applied on precoated silica gel GF254 plate (Merck) by Linomat V (Camag) using 100 μL syringe. Plate was developed in a mobile phase of toluene:ethyl acetate:formic acid:methanol (3:3:0.8:0.5 v/v/v/v). Developed plate was visualized and photographed in ultraviolet light at 254 nm and 366 nm using Camag Reprostar 3, Camag. The plate was derivatized with vanillin-sulfuric acid reagent and heated at 105°C for 10 min and then viewed under white light [Figure 1]; the Rf values were 0.56, 0.75, 0.76, and 0.74 for gallic acid, guggulsterone-E, guggulsterone -Z, and piperine, respectively.
From the spray drying operation, Triphala Kwath processed Guggulu, free-flowing powder, was obtained. This was blended with the excipients and DSC carried on this blend indicated [Figures [Figures22 and and3]3] that there is no interaction between the excipients and proposed tablet actives. Powder characteristics are vital for solid dosage forms and the result of micromeritic properties of these blends is summarized in Table 3. Tablets made from the blend Triphala Guggulu formulation (TGF)-3 were evaluated for tablet weight uniformity, crushing strength, disintegration test, and friability [Table 4].
In the classical preparations of Guggulu, different processing methods for different preparations are mentioned. Drying process impacts the quality of the formulation, and hence, practical implementation of these practices at commercial manufacturing needs critical process control parameters. Monitoring these parameters will help to control batch to batch variations. In the present study, we have used spray drying technology for drying of processed Guggulu. Use of this technology allows to control powder characteristics (for example - Bd, moisture, flow properties, etc.) and uniform formulation can be developed batch after batch. The powder blends were evaluated for compatibility studies by DSC [Figures [Figures22 and and3]3] which indicated the absence of any interaction between TG and excipients.
USP informs about the limits for powder flow properties, which helps for evaluating the flowability of powders, which is intended for compression into tablet dosage form. Using approved excipients in different combinations, we were able to achieve the required flow property [Table 3] as per USP. Based on these results of micromeritic properties, blend TGF-3 was selected for compression.
Compressed tablets were evaluated for their physical tablet characteristics and found to meet the USP requirements [Table 4]. Interestingly, the tablet disintegration time was <30 min and was pharmaceutically well within limit. This preparation is from Guggulu and hence is expected to show higher disintegration time. The Ayurvedic Pharmacopoeia of India (API) limit is of maximum 60 min and the presence of markers such as guggulsterone and piperine is ascertained using thin layer chromatography profile in both before and after derivatization.
Ayurvedic medicines are time tested and have capability to fulfill global requirements of wellbeing. In the current study, oleo-gum-resin of C. wightii is the major ingredient and possesses challenge for formulator as it increases the disintegration time of tablet. However, using the modern techniques of spray drying, the TG preparation was converted into free-flowing powder and developed into tablet dosage form meeting modern day regulations. This exercise can well be applied to other Guggulu formulations too.
There are no conflicts of interest.