title: Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.
abstract: The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.
authors.affiliation: Pharmaceutics International Inc., Hunt Valley, MD, USA.
authors.forename: Noorullah Naqvi
authors.initials: NN
authors.lastname: Mohammed
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Singh
authors.forename: Weibin
authors.initials: W
authors.lastname: Deng
authors.forename: Narasimha S
authors.initials: NS
authors.lastname: Murthy
authors.forename: Elanor
authors.initials: E
authors.lastname: Pinto
authors.forename: Divya
authors.initials: D
authors.lastname: Tewari
authors.forename: Thomas
authors.initials: T
authors.lastname: Durig
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004343:Drug Implants / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006245:Hardness Tests; D057927:Hydrophobic and Hydrophilic Interactions; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004337:Drug Carriers; D004343:Drug Implants; D005079:Excipients; D011108:Polymers; D013607:Tablets; D008353:Mannitol; D002482:Cellulose; D007660:Ketoprofen; C008079:hydroxypropylcellulose