title: Hot melt extrusion based solid solution approach: Exploring polymer comparison, physicochemical characterization and in-vivo evaluation.
abstract: The objective of this study was to develop solid solution (SSL) using hot-melt extrusion as a continuous manufacturing method. Powder blends of artesunate (ARS) a water insoluble drug with either Soluplus (SOL) or Kollidon VA64 (VA64) and additives in the form of surfactants or plasticizers were extruded to manufacture extrudes. The incorporation of surfactant or plasticizers facilitates smooth extrusion processing of the drug-excipient blend which directly reduced the residence time to form extrudes and works as parameter to control flow of the drug-excipients melt inside the extruder barrel. Differential scanning calorimetry (DSC) and X-ray diffraction (TXRD) analysis revealed the existence of the drug within the extrudes in amorphous state. Scanning electron microscopy (SEM), Raman spectroscopy (RS), Raman imaging (RI) and Atomic force microscopy (AFM) analytical characterization were carry out on the SSL formulations showed a homogeneous drug distribution within the extrudes. (2)D NMR and (1)H NMR studies were undertaken to reveal the possible drug-excipient interactions. The SSL produced via continuous HME processing showed significantly faster release of ARS compared to the pure drug substance. It is observed that F1 SSL (soluplus based) have 66.44 times higher AUC(0-72) and 16.60 times higher Cmax than pure ARS. Also K1 SSL (Kollidon VA64 based) have 62.20 times higher AUC(0-72) and 13.40 times higher Cmax than pure ARS.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, Maharashtra, India; Faculty of Pharmaceutics Department, H.K. College of Pharmacy, Relief Road, Oshiwara, Jogeshwari West, Mumbai 400102, Maharashtra, India. Electronic address: riteshphd.ict@gmail.com.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Fule
authors.affiliation: Faculty of Pharmacology Department, Vidyabharati College of Pharmacy, C.K. Naidu Road, SH 200, Camp, Amravati, Maharashtra 444602, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Paithankar
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, Maharashtra, India.
authors.forename: Purnima
authors.initials: P
authors.lastname: Amin
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077332:Artesunate; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D008297:Male; D010968:Plasticizers / Q000737:chemistry; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D005079:Excipients; D010968:Plasticizers; D011108:Polymers; D011145:Polyvinyls; D011759:Pyrrolidines; D013501:Surface-Active Agents; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D000077332:Artesunate
keywords: (2)D NMR; Artesunate; Atomic force microscopy; Bioavailability; Dissolution; Hot melt extrusion; solid solution