Development of Halal modified release gliclazide 60 mg tablets by central composite design and production by direct compression
Background: Gliclazide is a second generation sulphonylurea drug used for the treatment of type 2 diabetes mellitus. Commercially available modified release (MR) gliclazide tablet is a once-daily formulation that employs a hydrophilic matrix of a hypromellose for drug release retardant activity. It...
| Main Authors: | , , |
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| Format: | Conference or Workshop Item |
| Language: | English |
| Published: |
2014
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/38282/ http://irep.iium.edu.my/38282/ http://irep.iium.edu.my/38282/1/ICIP_2014.pdf |
| Summary: | Background: Gliclazide is a second generation sulphonylurea drug used for the treatment of type 2 diabetes mellitus. Commercially available modified release (MR) gliclazide tablet is a once-daily formulation that employs a hydrophilic matrix of a hypromellose for drug release retardant activity. It has similar efficacy but offers several advantages compared to the conventional immediate release tablets. It maintains the drug in plasma for longer duration and hence helps to achieve long-term glycaemic control. Hypromellose has the advantage of being a halal product of vegetable origin, physically stable over wide temperature and humidity ranges, with global regulatory acceptance and low toxicity. The registered patents use either wet or dry granulation to improve powder flow properties before compression. However, oproduction by direct compression reduces development and production time and thereby reduces manufacturing costs significantly. Methocel K100 LV DC2 Premium is a newly introduced direct compression grades of hypromellose that can be used for this purpose.
Objectives: To develop a hydrophilic matrix type modified release gliclazide 60 mg tablets by direct compression using newly developed Methocel® K100 Premium LV DC2 as the rate control polymer that have a dissolution profile with high similarity and low difference with the branded gliclazide. The aim is to produce commercially viable gliclazide 60 mg modified release tablets at affordable price and minimum production time.
Methods: Response surface methodology using central composite design was adopted for optimization of extended release tablets of gliclazide using one central, four factorial and four axial points and repeating central point 5 times to estimate the pure experimental uncertainty at the factor levels. The two independent formulation variables included the amount of Methocel® K100 LV (A) and Maltrin® M150 (B), whereas the response variables were cumulative % drug release in 1, 4, 8, and 12 hours. 13 formulations of 320 mg tablets containing 60 mg gliclazide were prepared by direct compression using rotary tablet machine (Remik-II, Karnavati Engineering Ltd., india). Prior to compression, powder flow properties were evaluated using tapped density, Carr’s index, and angle of repose. Compression force of the tablet machine was adjusted to produce tablets with hardness of 7-8 Kg. After compression, tablets were evaluated for hardness, weight variation, friability and in vitro dissolution were evaluated. Drug release data were fitted to various mathematical models for describing the release mechanism from tablets. The effect of percentage of polymer and maltodextrin on the percentage of drug release at different time points were statistically evaluated by applying one-way ANOVA at 0.05 level using a commercially available software package Design-Expert® version 6.05 (Stat-Ease, Inc.). The design was evaluated by linear model. Two more formulas were prepared to evaluate the prediction ability of the CCD model.
Results: The angle of repose indicated varying degrees of flowability from good flow to passable (33.17(±1.8) to 41.2 (±1.4)). Similarly, the Carr’s index results provided powders with excellent flow to passable (8.0 to 23%). All the formulations showed a high correlation coefficient (r2) with zero order and Krosmeyer-Pepas release mechanism. The effect of variables on the response followed linear model at 1, and 8 hours, while followed quadratic model at 4 and 12 hours. The actual cumulative % drug release versus predicted of the two formulations, F14 and F15, showed good model prediction with high similarity (87 and 98; respectively) and low difference factors (2 and 1 respectively). The optimized formula F14 and F2 were selected because of their high similarity factor and low difference factor with the branded gliclazide 60 mg MR tablets.
Conclusion: The results demonstrate the feasibility of direct compression for production of modified release tablets and the response surface methodology for its development.
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