title: Development of Extended-Release Oral Flexible Tablet (ER-OFT) Formulation for Pediatric and Geriatric Compliance: an Age-Appropriate Formulation.
abstract: Development of age-appropriate formulation suitable for pediatric and geriatric patients involves various challenges. The objective of this research was to develop extended-release oral flexible tablet (ER-OFT) formulation using carbamazepine (CBZ) as model drug for pediatric and geriatric compliance. ER-microparticles of carbamazepine, a BCS class 2, and narrow therapeutic index (NTI) drug, were prepared using ethyl cellulose as matrixing polymer and hypromellose as hydrophilic pore former. Microparticles were prepared using high-shear granulator fitted with an atomizing spray system. Granulation of carbamazepine and ethyl cellulose (EC-FP) with ethanolic binder solution resulted in ER-microparticles with extended-release >16 h. Release kinetics of ER microparticles showed Higuchi model by drug diffusion and erosion. Korsemeyer-peppas release exponent "n" value 0.42 suggested Fickian diffusion. ER-OFT was prepared by blending of ER-microparticles with water-insoluble compressible aid and disintegrating agent. ER-OFT was characterized for performance characteristics and elemental impurities. As the polymer content in formulation was <10%, the size of ER-OFT was smaller compared to marketed ER-formulations. ER-OFT showed in vitro disintegration time of <30 s as per USP and dispersion time of ∼60 to 180 s in 5 to 10 mL of water. Drug release profiles of ER-microparticles and ER-OFT were comparable as f2 values were >50. In vitro dissolution of ER-OFT was comparable to the marketed ER formulation in the pH range of GIT. ER-OFT can be orally swallowed, orally disintegrating, and used as dispersible tablets. Compared to non-disintegrating type ER-formulations, ER-OFT would provide uniform drug release in GIT with low within-subject variability an essential criterion for NTI drug.
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research, Bharathidasan Institute of Technology Campus, Anna University, Tiruchirappalli, TN, 620024, India.
authors.forename: Prabagaran
authors.initials: P
authors.lastname: Chandrasekaran
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research, Bharathidasan Institute of Technology Campus, Anna University, Tiruchirappalli, TN, 620024, India. hodpharma.aut@gmail.com.|National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries, Department of Pharmaceutical Technology, BIT Campus, Anna University, Tiruchirappalli, TN, 620024, India. hodpharma.aut@gmail.com.
authors.forename: Ruckmani
authors.initials: R
authors.lastname: Kandasamy
mesh_terms: D000369:Aged, 80 and over; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002648:Child; D003692:Delayed-Action Preparations; D004058:Diffusion; D004339:Drug Compounding; D065546:Drug Liberation; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry; D007700:Kinetics; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D002220:Carbamazepine; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; D002482:Cellulose
keywords: geriatrics; microparticles; narrow therapeutic index; oral flexible tablets; pediatrics