BackgroundOrlistat is an irreversible inhibitor of the lipase enzyme that prevents trigylcerides from being digested, thereby inhibiting triglyceride hydrolysis and absorption. The resultant reduced calorie uptake enables a positive effect on weight control. Systemic absorption of the drug is, therefore, not necessary for its mode of action. An alternative in vitro study (pharmacodynamic) has been introduced for this drug, as in vivo bioavailability studies are irrelevant with regard to the achievement of the product’s intended purposes.ObjectivesTo develop a new validated high-performance liquid chromatography (HPLC) method for the analysis of orlistat and to assess the potency and equivalence of three orlistat formulations using the pharmacodynamic method as a surrogate indicator of pharmaceutical interchangeability.MethodsA new HPLC method was developed for the analysis and for the dissolution studies of orlistat in capsules. Pancreatic lipase activity was measured for three different capsule products: Orlislim®, Slimcare®, and Xenical®, G1, G2, and the brand, respectively. Porcine pancreatic lipase and p-nitrophenyl butyrate (PNPB) were placed in a pH 7.4 reaction buffer at 37°C, and substrate hydrolysis was monitored by measuring absorbance changes at 410 nm; this was repeated on six capsules of each product. The inhibition was expressed by the concentration of product, which inhibited 50% of the activity of pancreatic lipase (IC50).ResultsThe new analytical method was suitable for orlistat analysis. Values of IC50 from regression lines and equations were 6.14, 8.43, and 7.80 μg/mL for Orlislim®, Xenical®, and Slimcare®, respectively.ConclusionPharmacodynamic studies of lipase inhibition could be used to support in vitro dissolution, which demonstrates interchangeability between generic and branded orlistat capsules. Moreover, it could be suggested as an alternative tool to bioequivalence studies for orlistat oral products.

ObjectivesThe objectives of this study were to evaluate the general quality of the most prescribed products of valsartan (VL; alone or in combination) and to evaluate their efficacy and safety among Palestinian population through in vivo postmarketing surveillance.Patients and methodsThe first part was pharmacopeial quality control assay, including dissolution, disintegration, friability, and weight uniformity for VL. The second part was a 3-month cardiology clinics, observational, postmarketing surveillance pilot study that included 103 hypertensive patients who were prescribed 80 mg or 160 mg of VL as monotherapy or combination therapy. The end points were reduction in blood pressure (BP) and the rate of incidence of adverse effects (AEs) at weeks 4 and 8.ResultsAccording to our quality control tests, all VL products showed high-quality standards according to the international guidelines. A reduction in BP was observed at weeks 4 and 8, and no significant difference was observed between the strengths of 80 mg and 160 mg. Higher BP reduction was observed after the use of combination therapy. Moreover, VL was well tolerated; most of the AEs were of mild-to-moderate intensity. In general, the most frequently reported AEs included headache (17.5%), dizziness (11.75%), and weakness (11.7%). No serious AEs or death cases were reported during the study period.ConclusionHigh quality of VL tablet products was used; hence, the observed efficacy and safety results should be related to patient’s factors and not due to any product defects or substandard quality. Moreover, VL is an effective treatment for essential hypertension.