Watnasirichaikul S, Arunothayanun P, Pirayavaraporn C, Eksaengsri A; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. A10240.

Research and Development Institute, Government Pharmaceutical Organization, Bangkok, Thailand

Background: In order to develop a clear ritonavir solution readily for filling in gelatin capsules, water and alcohol, which may help dissolving ritonavir but cause capsule deformation, are preferably avoided from the formulation. The solubility of ritonavir in suitable non-aqueous systems was studied and the obtained clear solution was identified for its ability to self-emulsify upon dilution with water. Methods: Ritonavir was dissolved at 60-80 [o]C for 15 minutes in single solubilizers, i.e. butylene glycol (BG), propylene glycol (PG), glyceryl monocaprylate (C8), or in binary mixtures (1:1 weight ratio) of BG/C8, BG/ethanol, and BG/polyethylene glycol 400 (PEG400). The maximum concentrations of ritonavir which can produce clear solutions in each system were recorded. Self-emulsifying ability of the obtained non-aqueous solutions added with polyoxyl 40 hydrogenated castor oil (PH40) was tested. The degradation of ritonavir as a function of temperature used in the solubilizing process was also studied using a HPLC. Results: For single solubilizers, C8 provided the highest solubility of up to 390 mg ritonavir in 1 g C8. Ritonavir was hardly dissolved in PG, while a maximum amount of 70 mg was dissolved in 1 g BG. The amounts of ritonavir dissolved in the binary mixtures were found to be 500, 200, and 125 mg in 1 g BG/ethanol, BG/C8, and BG/PEG400, respectively. Clear ritonavir solution in C8 or BG/C8 added with PH40 was found to self-emulsify upon dilution with water. HPLC revealed that higher amount of degradation products were detected when higher temperature was used for solubilization. Conclusions: A clear ritonavir solution consisting of ritonavir, BG, C8, and PH40 was successfully developed as a SEDDS in the absence of alcohol and water. The system forms emulsion on dispersing in water, which prevents drug precipitation and may improve drug absorption.

Publication Types:

• Meeting Abstracts

Keywords:

• Capsules
• Chemistry, Pharmaceutical
• Chromatography, High Pressure Liquid
• Drug Delivery Systems
• Ethanol
• Polyethylene Glycols
• Propylene Glycols
• Ritonavir
• Solubility
• Water

Other ID:

• GWAIDS0032084

UI: 102276298

From Meeting Abstracts