Design and Characterization of Nanocrystals of Lovastatin for Solubility and Dissolution Enhancement

Basavaraj K Nanjwade,Ganesh K Derkar,F.V Manvi,Veerendra K Nanjwade,Hiren M Bechra

doi:10.4172/2157-7439.1000107

Abstract

A major hurdle in pharmaceutical formulation is water insolubility of most of the drugs affecting stability and bioavailability of the drug, if the drug is also insoluble in organic medium, it is difficult to deliver the drug in a sufficiently bioavailable form and hence it is a great challenge to formulation researchers to overcome such difficulty. Although some approaches are available for enhancing the dissolution of poorly soluble drugs but has certain draw backs like low drug loading and large doses. However, a new solution to poorly water soluble drug candidates is now available i.e. nanonisation and it leads to much more soluble, more biologically available and safer dosage form of poorly soluble and poorly bioavailable drugs. In the present work, a nanocrystal of lovastatin was formulated by using simple precipitation method without using stabilizer or surfactant and it was found that formulation at 3 mM concentration of drug with the acetone and methanol as a solvent and at proper dilution (50 times) of drug solution with water, nanocrystals with less particle size is possible with slight change in crystallinity. It has also shown that, the drug has enhanced saturation solubility, increased dissolution rate and more bioavailable in biological fluid when drug formulated by using acetone and methanol as a solvent. Whereas drug formulation with acetonitrile has large particle size, less saturation solubility and low rate of dissolution.

Highlights

Aqueous solubility is one of the key determinants in development of new chemical entities as successful drugs
Surface morphology of the formed crystals was determined by using SEM and was found that crystalline nature of all the formulations remains with slight change in crystallinity
This evaluation was mainly carried out to check the effect of different solvents on particle size and it was found that the smallest particle size was observed in formulation F1 and F2 as compared to F3 formulation

Summary

Introduction

Aqueous solubility is one of the key determinants in development of new chemical entities as successful drugs. New drug development technologies, such as combinational chemistry and high throughput screening are based on the basic principles of medicinal chemistry, teaching that the most reliable method to increase in vitro potency is to add lipophilic moiety at appropriate position of the lead structure. This has led to an increase in the number of lipophilic and poorly soluble molecules being investigated for their therapeutic activity. Various formulation techniques are applied to compensate for their insolubility and consequent slow dissolution rate These include formulation of the amorphous solid form, nanoparticles, microemulsions, solid dispersion, melt extrusion, salt formation and formation of water soluble complexes [1]. On average, according to the tufts center for the study of drug development, only five out of every 5000 potential drugs are tested in clinical trials, and of these only one will eventually be approved for use in patients [2]

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Conclusion