title: Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance.
abstract: The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy.
authors.affiliation: Pharmaceutics Division, Dept. of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Pharmaceutics Division, Dept. of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kamboj
authors.affiliation: Pharmaceutics Division, Dept. of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Gursharan
authors.initials: G
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, Dept. of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India. Electronic address: vikas@pbi.ac.in.
authors.forename: Vikas
authors.initials: V
authors.lastname: Rana
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077608:Aprepitant; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D005947:Glucose / Q000737:chemistry; D007700:Kinetics; D008297:Male; D009025:Morpholines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010368:Pectins / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013649:Taste; D013718:Tensile Strength
chemical_list: D000932:Antiemetics; D004337:Drug Carriers; D009025:Morpholines; D000077608:Aprepitant; D010368:Pectins; D005947:Glucose
keywords: Bioavailability; Dissolution; Orally disintegrating films; Pullulan; Tamarind pectin; Tensile strength