Diabetes mellitus (DM) is a metabolic disorder characterized by a persistently elevated blood glucose associated with absent or inadequate pancreatic insulin secretion, with or without concurrent impairment of insulin action.1 There are two main types of diabetes, type 1 diabetes mellitus and type 2 diabetes mellitus. Type 2 diabetes mellitus is the most common form of diabetes and a rapidly growing health concern in both developed and developing nations.2, 3 It accounts for 90–95% of all person with diabetes and is expected to increase to 439 million by 2030. 4, 5 Among the treatment options existing, Metformin hydrochloride is the most widely used oral medication to treat type 2 diabetes worldwide. 3
Metformin hydrochloride, an oral anti-diabetic agent, acts by lowering both basal and postprandial plasma glucose. Other anti-diabetic agent such as sulfonylurea may induce hypoglycemia but metformin hydrochloride does not cause hypoglycemia at any reasonable dose and usually called anti-hyperglycemic agent. Metformin hydrochloride work as an insulin sensitizer; allowing the body in utilizing insulin and it’s classified under biguanide class.6–8
Metformin hydrochloride (N, N-dimethyl-imido-dicarbonimidic diamide hydrochloride) is small basic compound which has molecular weight of 129 Da and ionized at physiological PH.9 Even though metformin is hydrophilic base chemically, it’s usually present in an oral dosage forms in its hydrochloride salt form (Fig. 1). This chemical property shows that metformin has low lipophilic property and therefore, the diffusion of metformin through cell membrane is low. After oral administration, metformin is largely absorbed from the upper small intestine, and it undergoes limited systemic absorption with a half-life of about 3 hours. Therefore, repeated administration of the conventional metformin hydrochloride tablets is mandatory for effective treatment.10–12
According to Biopharmaceutical Classification System (BCS), metformin is classified under class III drugs.13 For such drugs, permeability is the rate-limiting step for drug absorption. Rapid dissolution is especially desirable to maximize the contact time between the dissolved drug and mucosal membrane. So that, the duration of dissolution should be strict. Hence, as drug permeation is rate-limiting, no in-vitro in-vivo correlation (IVIV) is expected. 14, 15
Pharmaceutical products containing the same active ingredient can be produced and marketed by many companies under different ‘brand’ name as a generic drug products once the patent for the innovator get expired. Generic and innovator products should be the same with respect to quality, safety, efficacy, strength, dosage form, route of administration and intended use.16– 18 The introduction of generic drugs from multiple sources into the markets improved availability and access to life-saving drug especially in developing countries. 19 In addition, these generic drugs are marketed with lower price and related with public health cost reduction.20, 21 Despite these benefits, generic products are also related with variety of problems which might place the customers’ health at risk. The interchangeability of generic drugs with the originator might still be questionable.
Quality is one of the most important criteria in guarantying optimal treatment out come from medicines and is presently receiving increased attention in generic manufacturing.22 Circulation of poor quality drug products in the international market increased significantly as a result of ineffective regulation of manufacturing and trading of pharmaceutical products.23 Therefore, the manufacturing, distribution, storage and use of drugs need to be regulated by authorized regulatory institutions.
Poor quality medicines are public health problems and affect both developing and developed countries.24, 25 The World Health Organization reported that 10% medical products in low and middle-income countries are either substandard or falsified 26 and Ethiopia is one of the low-income countries. Considering this, falsified or substandard medicines could be available in the drug market. Reasons for the supply of such drugs in low and middle income country could be attributed to weak regulatory enforcement, lack of informal market control, weak port control, poor cooperation between executive bodies and resource constraint. 27, 28 The availability of such types of drugs on the market might leads to treatment failure, increased mortality and morbidity, drug resistance and economic loss.29
For better health of the public, supplying good quality medicine is mandatory. But it is often missing in developing country like Ethiopia which has week regulatory system for pharmaceuticals. World Health Organization (WHO) has estimated that about 30% of the medicines on sale in Africa countries and parts of Asia and Latin America are counterfeit, while other developing countries have < 10%; overall, a reasonable range is between 10–30%.30 In 2013, the Public Health and Drug Testing Laboratory (PHDTL) tests 5000 drug samples from Bangladesh’s mammoth Pharmaceutical industry and according to this study, 60% of drugs are either counterfeit or of very poor quality.31
Generally, medicines used in health care need certain types of standards to have quality, safety and efficacy. So, monitoring drug quality through in-vitro test is mandatory to safeguard the health of the public as a whole and to reduce morbidity and mortality associated with poor quality medicines.32 In Ethiopia, there are very few pharmaceutical manufacturing companies and the country is principally dependant on imported pharmaceuticals. There are many multisource metformin hydrochloride tablets that are legally registered by Ethiopian food and drug administration and available on market for public use. Hence, there should be a means to determine that generic pharmaceutical products are therapeutically equivalent and interchangeable with their innovator’s as unpredictable clinical responses have been reported from similar drug products manufactured by different companies.33, 34 Therefore, this study was conducted to assess the in vitro equivalency of different brands of Metformin hydrochloride 500 mg tablet which are commonly available in drug retail outlet and hospital pharmacies in Jimma town and indiscriminately used in the treatment of diabetic patients. Six different brands of metformin hydrochloride 500 mg tablets that are available in jimma town were tested and compared for different physicochemical quality parameters including weight variation, friability, dissolution and assay.