Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Abstract

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.

Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

“…The processing temperatures of this polymer depend on its molecular weight and are in the range of 120-2008C [60]. Commercially available HPC, Klucel TM HPC polymers have been successfully used as matrix formers and solubilityenhancing agents [61].…”

“…PVP has been formulated by HME into DDS for numerous poorly water-soluble drug substances, for example indomethacin, nifedipin, lacidipine and tolbutamide [80,81]. Similarly, different grades of HPC have been used to prepare immediate-release oral dosage forms by HME [61]. Also, Copovidone 1 has been used for the production of solid dispersions by HME [82] to improve the bioavailability of many poorly water-soluble drugs [83,84].…”

Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion

“…Meanwhile, the extent of dissolution usually does not change significantly with tablets 4-7 although both increases [8][9][10] and decreases 6,7,11 were reported. Faster dissolution rates from tablets can be attributed either to a step decreasing the particle size before tableting 12 or to the fact that gelling of the polymer is less probable in tablets if each solid dispersion particle is dispersed completely allowing rapid wetting. 10 Another very important aspect is the maintenance of supersaturation during dissolution from a tablet, which can be challenging.…”

Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro–in vivo evaluations

“…1a). This design tends to impart improved solubility, which translates to improved bioavailability for BCS II APIs (Deng et al, 2013; Mohammed et al, 2012). However, the specific screw design is dictated by the particular properties that are desired in the final product, which is determined on a case-by-case basis.…”