Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

Abstract

To cite this article: Ahmed Khames (2017) Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique, Drug Delivery, 24:1, 328-338, DOI: 10.1080/10717544.2016 Department of Pharmaceutics and Pharmacy Technology, Taif University, Taif, Saudi Arabia Abstract BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/ Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 mg h/mL and 137.518 mg/mL in comparison to 321.011 mg h/mL and 38.673 mg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

DISSOLUTION AND SOLUBILITY ENHANCEMENT STRATEGIES: CURRENT and NOVEL PROSPECTIVES

“…Designing the liquisolid compacts by implementing mathematical model: -To desired for obtaining good flow behavior and compressibility of liquisolid systems or compacts a mathematical model is used to design for selecting of suitable carriers, solvents, and coating materials were proposed by Spireas A mathematical model is based on new fundamental properties of powder called flowable liquid retention potential (Ψ value) the Ψ value is defined as the max weight of the liquid that can be retained per unit [24,25].…”

Accelerated Dissolution Method to Facilitate In Vitro Evaluation of Risperidone-Containing Microspheres

“…where pK a (A) is the dissociation coefficient of the molecule, C(A) is the concentration of conjugated base of this molecule, and C(HA+) is the concentration of conjugated acid of this molecule (28). In this study, risperidone was a weak base, which can be ionized with decreasing pH when the total concentration of risperidone was constant.…”

Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film

“…Therefore, the pKa value, representing the extent of ionization at different pH is of great importance. Risperidone is a small molecule compound which has good lipophilicity and poor water solubility (Khames, 2017). It is a dibasic base with dissociation constants of 8.24 (pKa 1 ) and 3.11 (pKa 2 ) which is easy to ionize at the oral mucosa (Saibi et al, 2012).…”

“…It can also alleviate the symptoms of schizophrenia and improve the social and personal performance (Huang et al, 1993;de Leon et al, 2010). It is available as tablets, oral solutions, capsules, dispersible tablets, orally disintegrating tablets (ODTs), and ODFs in the dose strengths ranging from 0.5 to 4 mg (Khames, 2017). Taken orally, risperidone is completely and rapidly absorbed.…”