title: Liquid anti-solvent recrystallization to enhance dissolution of CRS 74, a new antiretroviral drug.
abstract: This study concerns a new compound named CRS 74 which has the property of inhibiting Human Immunodeficiency Virus (HIV) protease, an essential enzyme involved in HIV replication process. It is proved in this study that the original CRS 74 exhibits poor aqueous solubility and a very low dissolution rate, which can influence its bioavailability and clinical response. In an attempt to improve the dissolution rate, CRS 74 was recrystallized by liquid anti-solvent (LAS) crystallization. Ethanol was chosen as solvent and water as the anti-solvent. Recrystallized solids were compared with the original drug crystals in terms of physical and dissolution properties. Recrystallization without additives did not modify the CRS 74 dissolution profile compared to the original drug. CRS 74 was then recrystallized using different additives to optimize the process and formulate physicochemical properties. Steric stabilizer in organic phase ensured size-controlling effect, whereas electrostatic stabilizer in aqueous phase decreased particle agglomeration. Cationic additives avoided drug adsorption onto stainless steel T-mixer. In general, additive improved drug dissolution rate due to improvement of wetting properties by specific interactions between the drug and the additives, and ensured continuous production of CRS 74 by electrostatic repulsion.
authors: a Mines Albi, CNRS, Centre RAPSODEE, Université de Toulouse , Albi , France and.|b "Conception, Ingénierie et Développement de l'Aliment et du Médicament" (EA CIDAM), UFR Pharmacie, Université d'Auvergne , Clermont-Ferrand , France.
authors: Suênia
authors: S
authors: de Paiva Lacerda
authors: a Mines Albi, CNRS, Centre RAPSODEE, Université de Toulouse , Albi , France and.
authors: Fabienne
authors: F
authors: Espitalier
authors: b "Conception, Ingénierie et Développement de l'Aliment et du Médicament" (EA CIDAM), UFR Pharmacie, Université d'Auvergne , Clermont-Ferrand , France.
authors: Valérie
authors: V
authors: Hoffart
authors: a Mines Albi, CNRS, Centre RAPSODEE, Université de Toulouse , Albi , France and.
authors: Maria Inês
authors: MI
authors: Ré
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D008782:Methylurea Compounds / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: C000609252:CRS 74 compound; D005079:Excipients; D017320:HIV Protease Inhibitors; D008782:Methylurea Compounds; D012997:Solvents; D013844:Thiazoles; D000431:Ethanol
keywords: Additive; antiretroviral drug; bioavailability; dissolution rate; liquid anti-solvent crystallization; solubility