PREPARATION AND IN VITRO EVALUATION OF LACIDIPINE ORAL LIQUID SOLID TABLET AS AN APPROACH OF SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT

Nawal Ayash Rajab

doi:10.22159/ijap.2018v10i1.22313

Abstract

Objective: The aim of the present study was to prepare a new liquid-solid tablet to enhance the dissolution and bioavailability of a poor water soluble calcium channel blocker lacidipine.Methods: Firstly, solubility study of lacidipine in different media of water-miscible non-volatile solvents as tween 20, tween 80, propylene glycol, liquid paraffin, PEG200, PEG400, and PEG600 was investigated to select the most suitable solvent. A mathematical model was applied to calculate the appropriate amount of carrier and coating material.Four liquid-solid tablets of 6 mg lacidipine were prepared by dissolving the drug in the previously chosen water miscible non-volatile solvents, then a binary mixture of the carrier (Avicel PH 102) and coating material (Aerosil 200) at a ratio of 45:1 was used in all preparation since it gave the optimal flow property. Croscarmellose and magnesium stearate were incorporated in all prepared formulas as super disintegrant and lubricant respectively. On the other hand, directly compressed lacidipine tablet of the same previous composition without the addition of any non-volatile solvent was prepared for comparism study. Both characterizations of powder mixture and post-compression tablet evaluations were done. Differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were investigated for the pure drug, physical mixture, and selected liquid-solid tablet to exclude any drug-excipients interaction.Results: The obtained results indicated that PEG 200 was the most suitable solvent with lacidipine solubility of 2.81 mg/ml. Flowability of all the prepared formulas was found to be within the specification limits. The liquid-solid tablet formula with PEG 200 at 10% w/w lacidipine was the most suitable one in the term of disintegration time (21±0.2 second), 100% of drug release within 10 min, and with accepted other tablet properties.DSC thermograms for both physical mixture of selected liquisolid system and its tablets illustrated the formation of lacidipine amorphous solid solution. The absence of chemical interaction between drug and other formula components was confirmed by remaining all characteristic peaks of lacidipine in all investigated FTIR spectra.Conclusion: Liquid-solid tablet was considered as a promising system to enhance solubility and dissolution rate of poor-water soluble lacidipine.

Highlights

The poor dissolution rate of water-insoluble drugs is still a substantial problem confronting the pharmaceutical industry
The obtained results indicated that PEG 200 was the most suitable solvent with lacidipine solubility of 2.81 mg/ml
Differential scanning calorimetry (DSC) thermograms for both physical mixture of selected liquisolid system and its tablets illustrated the formation of lacidipine amorphous solid solution

Summary

Introduction

The poor dissolution rate of water-insoluble drugs is still a substantial problem confronting the pharmaceutical industry. A great number of new and possibly, beneficial chemical entities do not reach the public merely because of their poor oral bioavailability due to inadequate dissolution [1]. Due to their low bioavailability, poorly water-soluble drugs cause many difficulties in the development of pharmaceutical dosage forms for oral delivery [2]. Different techniques have been published in the scientific literature to enhance the dissolution profile and the absorption efficiency and bioavailability of water-insoluble and/or liquid lipophilic drugs. Its main advantages include simplicity of manufacturing, use of commercially available excipients, and application of well-known methods and equipment utilized for the manufacturing of conventional tablets [5]

Methods

Results

Conclusion