BIOWAIVER STUDY OF IMMEDIATE RELEASE GLIMEPIRIDE TABLETS

Objective: Demonstrating therapeutic equivalency regarding the efficacy and safety among originator products and generics is a key step in permitting the marketing of generic products. The study aimed to evaluate the bioequivalence of five different generic brands of Glimepiride tablets under biowaiver conditions. Methods: The quality of the tablet products, including uniformity of weight, friability, and disintegration test, was assessed using the United State Pharmacopeia (USP) general monograph for the tablet dosage form. The content of glimepiride in the tablets was measured using UV spectrophotometer at the wavelength 229 nm. The release of Glimepiride from the tested and originator tablet products was evaluated using the dissolution profiles conducted in HCI buffer pH 1.2, and phosphate buffer pH 6.4 and 7.8 by USP dissolution apparatus II. The bioequivalence of test products was assessed using the similarity and difference factors. Results:The tested products complied to USP requirements for quality standards; all the products show rapid disintegration, D1 show higher time (Three minutes) while D3 show lower time (28 seconds). The content of test products was (104.68, 93.75, 97.21, 97.03, and 102.10) for D1, D2, D3, D4, and D5 , respectively, compare to 103.70 for OB. Dissolution profiles revealed that the highest similarity to the originator was showed in pH 6.4; f2 ranged (74.5-68.4) for all the tested products and low similarity in pH 7.8; f2 ranged (45.2-64.7). Conclusion: The study showed that the generic products has noticeable similarity with the originator brand and it can be interchangeable.

Therapeutic Equivalency of Low-Molecular-Weight Heparins

OBJECTIVE: To review the recent literature on the approved uses of enoxaparin, dalteparin, ardeparin, and tinzaparin and the evidence for therapeutic equivalence. DATA SOURCES: A MEDLINE search (1993–January 2001) was conducted to identify English-language literature available on enoxaparin, dalteparin, ardeparin, and tinzaparin. STUDY SELECTION: All controlled trials evaluating low-molecular-weight heparins (LMWHs) versus standard therapy powered to detect a significant difference were reviewed. DATA EXTRACTION: Agents were reviewed with regard to safety and efficacy. DATA SYNTHESIS: As a class, LMWHs have chemical, physical, and clinical similarities. LMWHs have greater bioavailability, longer half-lives, a more predictable pharmacologic response, possible improved safety, and similar or greater efficacy compared with unfractionated heparin (UFH). Because of this, enoxaparin, dalteparin, ardeparin, and tinzaparin are being considered as alternatives to UFH or warfarin, and there is potential for therapeutic interchange. Evaluation of clinical trials is limited because of differing diagnostic methods, drug administration times, dose equivalencies, and outcome measurements. CONCLUSIONS: Only 1 trial has evaluated 2 LMWHs in a direct comparison in the same study. There is insufficient evidence for determining the therapeutic equivalence of LMWHs.

Therapeutic Assessment of Slow-K and K-Tab Potassium Chloride Formulations in Hypertensive Patients Treated with Thiazide Diuretics

Therapeutic equivalency among different drug products is one of the major issues confronting many clinicians today who are functioning as members of pharmacy and therapeutic committees and state Medicaid programs (SMP). Selection of one of the available slow-release potassium chloride formulations for inclusion in a hospital formulary or SMP exemplifies one of these therapeutic equivalency issues. To evaluate this issue, we studied 20 hypertensive adult patients receiving hydrochlorothiazide 50 mg/d to determine if there are significant differences between the administration of 24 mEq of Slow-K given as 8 mEq/tablet tid, and 30 mEq of K-Tab given as a 10 mEq/tablet tid. The study was conducted in a randomized, open-label, crossover design in which the two drug formulations of potassium chloride were compared over two four-week treatment periods. Results from this study indicate that 24 mEq of Slow-K and 30 mEq of K-Tab were equally effective in maintaining serum electrolyte concentrations, blood pressure measurements, and electrocardiogram evaluations within normal limits in all 20 hypertensive patients studied. Furthermore, no adverse effects were noted with either potassium chloride formulation, and patient acceptance, tolerability, and compliance to prescribed dosing regimens were similar for both products. Based on our findings, therefore, we conclude that 24 mEq of Slow-K and 30 mEq of K-Tab given three times daily as 8 mEq and 10 mEq tablets, respectively, are therapeutically equivalent.