Dissolution Test For Metformin Hydrochloride Tablets
Prepare the test specimen as follows. Grind 5 Tablets to a fine powder. Add 25 mL of water, and shake for 5 minutes. Add 25 mL of chloroform, and shake for an additional 5 minutes.
Centrifuge at 2500 rpm for 5 minutes. Transfer the lower chloroform layer to another container, evaporate the solvent under a stream of nitrogen, and dry the extract at 60 for 3 hours: the IR absorption spectrum of a potassium bromide dispersion prepared from the residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of.
Chromatographic system (see )The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.5 mL per minute.
The column temperature is maintained at 30. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 5000 theoretical plates; the tailing factor is between 0.8 and 2.0; and the relative standard deviation for replicate injections is not more than 2%. Chromatographic system (see )The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7.
The flow rate is about 1.2 mL per minute. The column temperature is maintained at 40. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: for the peak due to glyburide, the capacity factor, k ¢, is not less than 7; the column efficiency is not less than 3000 theoretical plates; and the relative standard deviation for replicate injections is not more than 1.5%. For the peak due to glyburide related compound A, the relative retention time is approximately 0.30 with respect to glyburide; and the relative standard deviation for replicate injections is not more than 10%. Chromatographic system (see )The liquid chromatograph is equipped with a 218-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1.
The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30.
IntroductionMetformin is an oral antidiabetic drug (OAD) belonging to the biguanide class. Other biguanides are phenformin and buformin, but the former was withdrawn from market due to reported links with serious cases of lactic acidosis., Metformin, however, remains the drug of choice in the management of type 2 diabetes mellitus, particularly in patients whose renal functions have not been compromised. According to the United Kingdom Prospective Diabetes Study (UKPDS), metformin is superior to other OADs in lowering both the macrovascular- and microvascular-related complications that characterize the disease progression in diabetic patients., Recently, some researchers have spoken out against the claims by UKPDS, citing methodological shortcomings. Despite this dichotomy, metformin remains a first-line drug in obese and non-obese diabetic patients, alongside lifestyle adjustment.
It is considered superior to sulphonylurea because it causes no weight gain and it is rarely associated with hypoglycaemia., Moreover, it is safer than the thiazolinedidiones because it offers a cardio-protective effect instead of cardiotoxicity.,Metformin, 1,1-dimethylbiguanide , has a low molecular weight (129.1 g/mol), good solubility (about 300 mg/mL) in polar solvents, resulting in solution with pH range of 1.2–6.8 at 25 °C; however, its lipophilicity and permeability are unacceptably low. Metformin is provided as 500, 850 and 1,000 mg tablets, either as immediate release (IR) and extended release (ER) formulations. Glucophage® (a descriptive name to describe its role as a ‘glucose-eater’) is an innovator product that stands out in terms of quality and efficacy over time, but is relatively unaffordable for some patients. In general, the high-price associated with some branded products may predispose patients to opt for generic products, often registered by the drug regulatory body.
In Nigeria, many generic products are in circulation, and they are often preferred by the populace because of the prevailing poor socio-economic status. This trend has helped to curtail rising in pharmaceutical expenditure, especially in low- to middle-income countries. However, generic substitution should not be based solely on the initial cost of treatment but on the overall cost effectiveness of pharmacological treatment. As a result, a standard has been set for generic substitution. Interchangeability is permitted when the generic product demonstrates bioequivalence (BE) and therapeutic equivalence with the innovator. 1 Chemical structure of metformin.BE of a generic product could be determined by either in vivo or in vitro studies.
In vivo BE studies are frequently used to establish therapeutic equivalence, but this approach is usually expensive and more rigorous and may require clinical trial or study expertise. In vitro dissolution profiles are proxies for establishing BE when the drug meets the criteria prescribed for a Biopharmaceutics Classification System (BCS) biowaiver. The BCS considers three major factors–dissolution, solubility and intestinal permeability–which influence the rate and extent of drug absorption from IR solid oral dosage forms. Metformin is highly soluble in water with poor permeability, and as such it is classified as a BCS class 3. It may enjoy a biowaiver if dissolution of 85% or more of the labelled amount of the active pharmaceutical ingredient (API) in both the generic and the innovator products is attainable within 15 min in standard dissolution media at pH 1.2, 4.5 and 6.8.An in vitro dissolution study on four generic products of metformin showed that none of the four brands of metformin tested met this requirement because the innovator product and two others did not achieve 85% dissolution in 15 min. In a similar study conducted by Olusola et al. In 2012 on eight generic products of metformin, only three met the criteria for BCS biowaiver after a physiochemical equivalence testing.
Dissolution Test For Metformin Hydrochloride Tablets 500 Mg
Thus, using an in vitro dissolution profile as a surrogate for in vivo BE is still debatable as in vivo-in vitro correlation has not been established for metformin in most cases. Developing countries will benefit from generic products, unfortunately the resources for testing drug quality is limited. App android game.
Thus, this study aimed to assess the bioavailability of generic formulations of metformin versus that of the innovator product. Materials and methods MaterialsMetformin HCl was obtained from AK Scientific chemicals (United States), high-performance liquid chromatography (HPLC) grade acetonitrile and methanol were obtained from Scharlau® Chemicals (Spain).
Cimetidine and potassium hydrogen phosphate were purchased from Sigma-Aldrich® Chemical Company (Germany). The innovator product of metformin (coded as A) and 13 other generic products of metformin tablets (coded as B, C, D, E, F, G, H, I, J, K, L, M and N) were purchased from retail pharmacies in Ile Ife, Ilesa and Ibadan South-West, Nigeria. ProductWeight Uniformity TestUV-Assay (% Content)Dissolution (% Released)After 15 MinAfter 45 MinAPass96.170.6 ± 0.2085.3 ± 0.15BPass100.086.7 ± 0.2791.6 ± 0.67CPass96.182.9 ± 0.2186.4 ± 0.14DPass93.944.6 ± 3.1256.25 ± 0.10EPass98.678.8 ± 0.2084.2 ± 0.35FPass100.276.5 ± 0.1987.5 ± 0.16GPass92.981.0 ± 0.3686.6 ± 0.29HPass98.558.0 ± 1.4684.0 ± 0.11IPass99.855.5 ± 0.7888.4 ± 0.46JFail95.267.5 ± 0.5086.2 + 0.16KPass100.22.5 ± 0.172.8 ± 0.04LPass95.687.7 ± 0.2289.1 ± 0.12MPass95.384.6 ± 0.2387.6 ± 0.06NPass101.489.0 ± 0.0689.6 ± 0.38. For lack of resources, only product B was considered for in vivo comparative study. Seventeen healthy volunteers, including six females and eleven males, completed the in vivo study.
Treatment with both generic and innovator products was well tolerated. Metformin was quantifiable in all the subjects from 30 min to 10 h post-dose sampling points. The bioanalytical procedure for metformin analysis was validated based on FDA/CDER guidelines.
The LOD and LOQ were 10.2 and 30.9 ng/mL respectively. Accuracy, recovery and intra-day and inter-day precision are presented in. The average plasma concentrations-time profile of metformin for the innovator (reference) and the generic (test) products is depicted in.
Derived pharmacokinetic parameters, 90% CI and geometric mean ratio (GMR) of the test/reference products for logarithm-transformed BE parameters ( C max, AUC 0–10 hr and AUC 0–∞) are presented in. Abbreviations: CI, confidence interval; GMR, geometric mean ratio. DiscussionOut of 14 brands of metformin tablets in the Nigerian market, 10 products were found to be fit according to weight uniformity test, UV-spectrophotometric quantitative analysis and dissolution test. Eight of those products were generic and they were found to demonstrate pharmaceutical equivalence with the innovator brand by releasing 75% or more within 45 min using a basket rotating at 100 rpm. The products could have enjoyed in vivo biowaiver but some, including the innovator brand, were not sufficiently released in pH 6.8 phosphate buffer during the dissolution test to meet the specification of 85% or more release within 15 min.Metformin is highly hydrophilic, with poor permeability and it belongs to class III of BCS. To establish in vitro BE -in vivo BE correlation, metformin products should release ≥85% of API within 15 min.
The reason for this is that if the products rapidly dissolved under all physiological conditions, one will expect such products to behave like oral solutions in vivo. Only three generic products released ≥85% of its API within 15 min. This pattern was similar to that of previously reported dissolution studies on metformin tablets in Nigeria, where the products were noted not to be rapidly dissolving in any of the three media having pH 2.0, 4.5 and 6.8., The feasibility of generic substitutions of OAD with the same amount and quality of API in the management of diabetes relies on the fact that the products are therapeutically equivalent and are able to offer glycaemic control of.