Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Marco Vinicius Chaud,Maria Ondina Paganelli,Andréa Cristina De Lima,Pollyanna Tamascia,Maria Palmira Daflon Gremião,Osvaldo De Freitas

doi:10.1590/s1984-82502010000300010

Abstract

The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction.

Highlights

With the advent of high throughput screening (HTS) for agents with potential therapeutic value, the number of candidate drugs which are poorly soluble in water has increased considerably
The intestinal absorption of solid state pharmaceuticals depends upon two processes which should occur in a consecutive fashion: (1) dispersion of the pharmaceutical in the gastrointestinal tract, and (2) transport of the dispersed pharmaceutical through the blood
When the rate of dispersion of the pharmaceutical is significantly lower than the absorption rate, this becomes the limiting step in the absorption process

Summary

Introduction

With the advent of high throughput screening (HTS) for agents with potential therapeutic value, the number of candidate drugs which are poorly soluble in water has increased considerably. One of the first publications on the concepts and advantages of solid dispersion formulas was published by Sekiguchi and Obi in the late 1970s (Sethia, Squillante, 2003) In their publication these authors presented a new method for reducing the size of poorly soluble particles in water by formation of eutectic mixtures. Saito et al (2002), showed an increase in the solubility of griseofulvin using saccharides as carriers Other carriers such as lactose, micro crystalline cellulose, chroscarmellose sodium, amide of sodium glycolate, polymethacrylates, have been used to improve the absorption of pharmaceuticals that are poorly soluble in water (El-Arena et al 1998; Cornier et al 2000; Chowder et al, 2000; Babu et al 2002; Law et al, 2003; Mitchell et al, 2003, Ohara et al, 2005; Karavas et al, 2007; Kim et al, 2008). The objective of this study was to prepare solid dispersions by fusion and co-precipitation and evaluate, in vitro, the influence of these preparations of PZQ on solubility, dissolution rate, and intestinal absorption

Objectives

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Results

Conclusion