In Vitro Drug Release Testing Method For Nepafenac Ophthalmic Suspension.

In vitro release test (IVRT) method is important to monitor batch-to-batch quality variations during pharmaceutical manufacturing and also to show the pharmaceutical equivalence of a generic product with the innovator. To fulfil regulatory requirements for approval of a generic ophthalmic suspension product, in vitro release study is required. No compendial or non-compendial method is available for IVRT of nepafenac ophthalmic suspension. Current research is aimed to screen various approaches using different conventional and non-conventional instruments to suggest the most suitable technique appropriate for nepafenac ophthalmic suspension followed by optimization of method parameters and validation. The trials used the paddle apparatus (USP Type-2) with dialysis sacs, the flow-through cell apparatus (USP Type-4), the rotating bottle apparatus, and the Franz diffusion cell apparatus. With the USP Type-4 apparatus drug release was found to be ∼ 83% in the simulated tear fluid (STF) of pH 7.4 in 120 min that increased to ∼ 97% upon the addition of surfactant sodium lauryl sulfate (SLS). With USP Type-2 and Franz diffusion cell apparatus, the drug release was either slow or not reaching close to the complete release. Whereas, in the case of the rotating bottle apparatus, a burst release profile was observed. The estimation of the drug release was done by the HPLC method and all the method validation parameters like specificity, accuracy, linearity, and precision were found to be within acceptance criteria.

Simple RP-HPLC method for determination of triple drug combination of valsartan, amlodipine and hydrochlorothiazide in human plasma.

A simple RP-HPLC method for the quantification of valsartan (VAL), amlodipine (AML) and hydrochlorothiazide (HCT) in human plasma was developed and validated. VAL, AML and HCT were resolved using a Gemini C18 column and mobile phase gradient starting from 20 % acetonitrile and 80 % 10 mmol L(-1) ammonium formate (V/V, pH 3.5 ± 0.2, by formic acid) to 70 % acetonitrile and 30 % 10 mmol L(-1) ammonium formate, over 20 minutes, with a flow rate of 1 mL min(-1). The samples were purified by protein precipitation and extraction. Telmisartan was used as internal standard. The method was validated according to USFDA and EMEA guidelines with good reproducibility and linear responses R = 0.9985 (VAL), 0.9964 (AML), and 0.9971 (HCT). RSDs of intra- and inter-day precision ranged 2.2-8.1 and 4.6-11.7 %, respectively, for all three drugs. Mean extraction recoveries of three QCs for the triple drug combination were 76.5 (VAL), 72.0 (AML) and 73.0 (HCT) % for human plasma. Although the LC-MS/MS method is more sensitive than HPLC, HPLC is still suitable for preliminary pharmacokinetic study. The experiments performed demostrated that simultaneous determination of all components of the triple drug combination in human plasma can be done by this method. Proposed method can be also used for guidance to the LC-MS/MS method.