Abstract
Objective: To improve dissolution properties of atazanavir sulphate by preparing gastro-retentive granules by solid dispersion method and development of RP-HPLC method for estimation of this drug.Methods: Estimation of atazanavir sulphate was done using high performance liquid chromatography (HPLC) on inertsil column (5 µm, 250x4, 6 mm) with a mobile phase consists of methanol: water (91:9 v/v), at 0.5 ml/min flow rate and 249 nm UV detection. The method was validated as per ICH guidelines. Selection of the carrier for gastro-retentive formulation was based on phase solubility study of the drug. Solid dispersions of gastro-retentive granules of different composition of drug and carrier, were prepared by the kneading, heating and solvent evaporation. A 32factorial design was applied to optimize the gastro-retentive formulation. The amounts of polyethylene glycol 6000 (PEG 6000) (X1) and hydroxypropyl methyl cellulose (HPMC) (X2) were selected as independent variables and in vitro-release at 5, 9 h and total floating time was selected as dependent variables. Results: HPLC method was found to be linear in a concentration range of 10-60 μg/ml of the drug (r2= 0.999). The low value of % RSD in precision study indicates reproducibility of the method. The low value of LOD and LOQ suggests the sensitivity of the method. The solubility enhancement study of drug with various carriers followed descending order of solubility [Gelucire 44/14>PEG 6000>polyvinyl pyrrilidone (PVP)]. Highest % cumulative release was observed for the heating method at drug polymer (PEG 6000) ratio 1:5. Hence, this ratio has been selected for preparation of solid dispersion. From comparison of dissolution profile of formulated batches, formulation F4 [containing PEG6000 (1.6 g) and HPMC (200 mg)] showed promising dissolution parameters with desired floating properties.Conclusion: Results obtained by validation studies suggested that the developed HPLC method is simple, accurate, precise and can be used for routine analysis of atazanavir sulphate formulation. Results of evaluation of prepared batches indicate that batch F4 is a promising formulation for gastro-retentive dosage form of drug.
Highlights
Approx. 35 million people were died from acquired immuno deficiency syndrome (AIDS) related illnesses since start of the epidemic and about 36.7 million people were living with human immunodeficiency virus (HIV) infection during December 2015 throughout the world
This paper presents formulation development of gastro-retentive granules of atazanavir sulphate as well as development and validation of RP-high performance liquid chromatography (HPLC) method for estimation of this drug
Results from analysis of variance (ANOVA) (Response Surface Linear model) for cumulative % release of 5, 9 h and total floating time are given in table 13, 14, 15 respectively and their respective counter plots are given in fig. 9, 10, 11, respectively
Summary
Approx. 35 million people were died from acquired immuno deficiency syndrome (AIDS) related illnesses since start of the epidemic and about 36.7 million people were living with human immunodeficiency virus (HIV) infection during December 2015 throughout the world. 35 million people were died from acquired immuno deficiency syndrome (AIDS) related illnesses since start of the epidemic and about 36.7 million people were living with human immunodeficiency virus (HIV) infection during December 2015 throughout the world. The number of HIV infected patients is increasing every year [1]. In this context, an effective drug therapy is needed for the treatment of this infection. Atazanavir sulphate is a novel azapeptide HIV protease inhibitor with high specificity which prevents multiplication of HIV [2]. Atazanavir sulphate is an antiretroviral drug which belongs to BCS class-2 drugs, associated with poor solubility. Atazanavir sulphate has less bioavailability due to pH-dependent solubility and absorption [4, 5]
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