Comparative in Vitro Dissolution Study on Metformin Market Products Using Different Dissolution Apparatuses

Abstract

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products.Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured. Results:Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability. Conclusion:Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.

In Vitro Release Performance of Metformin Hydrochloride Formulations Using the Flow-Through Cell Method

“…Cell size, glass beads and flow rate are critical factors to form a special dissolution pattern useful to compare the in vitro release performance of drug products. Results agree with those reported by Hashem et al, [13] where after working with four commercial products (850 and 1000-mg), phosphate buffer pH 6.8 and the USP paddle apparatus (100 rpm) and flow-through cell method (laminar flow at 8 ml/min) a slower dissolution rate was found with the flowthrough cell. On the other hand, the absolute bioavailability of metformin when given orally is 50 -60% [16].…”

“…Additionally, five formulations showed f2>50 when were compared to the reference (500-mg) but data were calculated with six replicates of each formulation. Similar results were obtained by Hashem et al, [13] that worked with four drug products and two generics achieved f2>50 also with six replicates by drug product. One condition to calculate f2 similarity factor is the number of dosage units, it must be calculated with an average of 12 units [6].…”

“…Data were obtained with the study of seven commercial formulations (500-mg) with USP paddle apparatus at 75 rpm and 900 ml of simulated intestinal fluid pH 6.8 as dissolution medium. Hashem et al, [13] found DE values of 54.65 to 58.85%. They worked with two references (850-mg) and two generic products (1000-mg) using the USP paddle apparatus at 100 rpm and 900 ml of phosphate buffer pH 6.8.…”

“…About in vitro dissolution studies of metformin hydrochloride commercial formulations, several authors have reported limited works with the USP basket apparatus [8,9]. Other manuscripts describe the use of USP paddle apparatus [10][11][12][13][14][15][16] and only one has reported data with the flow-through cell method [13]. Most of them agree with the use of phosphate buffer pH 6.8 as dissolution medium, while others have tested metformin hydrochloride tablets with simulated intestinal fluid pH 6.8 [10] and dissolution media within physiological pH range (pH 1.2 -6.8) [11,12].…”

“…The use of the flow-through cell method to study metformin hydrochloride commercial formulations was only reported by Hashem et al, [13]; the dissolution equipment was used with laminar flow, cells of 22.6 mm and phosphate buffer pH 6.8 as dissolution medium. Two generic formulations (1000-mg) showed f2>50 but the reference was a drug product with a different dose (850-mg) and data were calculated with only six dosage units per drug product.…”