ABSTRACT
OBJECTIVES: The aim of the current research project was to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (Klucel™ ELF, EF, and LF) produced using hot-melt extrusion (HME) techniques and to assess the plasticization effect of P-CO2 on the various polymers tested. METHODS: The physico-mechanical properties of extrudates with and without injection of P-CO2 were examined and compared with extrudates with the addition of 5% liquid plasticizer of propylene glycol (PG). The extrudates were milled and compressed into tablets. Tablet characteristics of the extrudates with and without injection of P-CO2 were evaluated. RESULTS AND CONCLUSION: P-CO2 acted as a plasticizer for tested polymers, which allowed for the reduction in extrusion processing temperature. The microscopic morphology of the extrudates was changed to a foam-like structure due to the expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared with the extrudates processed without P-CO2 due to the increase of porosity and surface area of those extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates was increased and the percent friability was decreased. Thus, the good binding properties and compressibility of the extrudates were positively influenced by utilizing P-CO2 processing.
Subject(s)
Carbon Dioxide/chemistry , Cellulose/analogs & derivatives , Drug Compounding/methods , Ketoprofen/chemistry , Plasticizers/chemistry , Calorimetry, Differential Scanning , Cellulose/chemistry , Drug Carriers/chemistry , Drug Liberation , Hot Temperature , Ketoprofen/administration & dosage , Ketoprofen/pharmacokinetics , Particle Size , Polymers/chemistry , Porosity , Pressure , Solubility , Tablets , ThermogravimetryABSTRACT
The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly.
Subject(s)
Caffeine/adverse effects , Citrates/adverse effects , Taste/drug effects , Caffeine/chemistry , Cellulose/analogs & derivatives , Chemistry, Pharmaceutical , Citrates/chemistry , Drug Carriers , Drug Compounding , Humans , Plasticizers , Solubility , Tablets , Taste PerceptionABSTRACT
The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets.
Subject(s)
Drug Carriers/chemistry , Drug Compounding/instrumentation , Excipients/chemistry , Models, Biological , Piperazines/chemistry , Polymers/chemistry , Saliva/chemistry , Sulfonamides/chemistry , Acetates/chemistry , Cellulose/analogs & derivatives , Cellulose/chemistry , Drug Carriers/administration & dosage , Drug Carriers/adverse effects , Equipment Design , Gastric Juice/chemistry , Hot Temperature , Humans , Phosphodiesterase 5 Inhibitors/administration & dosage , Phosphodiesterase 5 Inhibitors/adverse effects , Phosphodiesterase 5 Inhibitors/chemistry , Piperazines/administration & dosage , Piperazines/adverse effects , Povidone/analogs & derivatives , Povidone/chemistry , Purines/administration & dosage , Purines/adverse effects , Purines/chemistry , Sildenafil Citrate , Solubility , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Surface Properties , Tablets , Taste , Vasodilator Agents/administration & dosage , Vasodilator Agents/adverse effects , Vasodilator Agents/chemistryABSTRACT
The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied.
