Preparation Process and in vitro release performances of HPMC-coated systems for pulsatile release of verapamil

The aim of this work was to evaluate the preparation process and in vitro release performances of HPMC coated systems for pulsatile release, containing verapamil as the active ingredient. Tableted cores of different size, formulated either for an immediate or prolonged drug liberation, were investigated in order to possibly meet diverse needs connected with the chronotherapy of ischemic heart disease, mainly occurring around awakening time.Tablets containing different amounts of verapamil hydrochloride were obtained by rotary press (AM8S, Ronchi, I) and coated with HPMC (Methocel\uaeE50 8% w/v aqueous solutions) in a tangential-spray rotary fluid bed (GPCG 1.1 Glatt\uae, D) equipped with a Teflon-coated disk. Release tests (n=3) were performed in a three-position USP28 disintegration apparatus (DT3, Sotax, CH; 800 ml distilled water, 37.0\ub10.5\ub0C). A single test unit was placed in each basket-rack assembly. Fluid samples were withdrawn automatically at fixed time points. Acetaminophen was quantified by spectrophotometer.The selected operating conditions allowed a feasible, high-yield process to be performed on the tablets in exam. Moreover, thanks to the relative flexibility of the coating technique, only minor modifications were introduced when coating different size cores. The in vitro release tests carried out on immediate release tablets with increasing coat thickness showed a typical lag phase preceding the prompt release of verapamil. Delayed release performances dependent on the coating level were also exhibited by systems prepared starting from prolonged release cores. From such systems, as pursued, the drug was released slowly over an extended time period. For all system typologies, a linear relationship was found between lag time and the applied amount of coating polymer.The results obtained in terms of low-viscosity HPMC-based aqueous spray-coating feasibility and programmable delayed release behavior seem to point out a potential suitability of the system for evening-dosing chronotherapy of ischemic heart diseas

Insulin-Containing oral time-dependent colon delivery system (Chronotopic) : evaluation of feasibility, in vitro release performances and stability

Purpose. To investigate the preparation, in vitro performances and stability of a previously proposed oral time-dependent device for colon delivery containing insulin. The system under investigation consists of a drug-containing core and a release-delaying hydroxypropyl methylcellulose (HPMC) layer. An outer enteric film would also be required to target the colon according to the time-based approach. Methods. Immediate release tablets (diameter: 5mm, 80mg) containing 2 mg of bovine insulin (57.6 IU) were coated up to 800 \u3bcm in a top-spray fluid bed (temperature of fluidized cores: 36-38\ub0C) with HPMC 2910 in 8.0% w/v aqueous solution. For stability studies, insulin specimens, powder mixture samples, tablet cores and HPMC-coated systems were stored at 4\ub0C or 25\ub0C and 60% RH. Assays were performed monthly by HPLC according to Ph. Eur. 5th Ed methods. Release tests (n=3) were carried out in phosphate buffer pH 6.8 at 37\ub10.5\ub0C. Results. There was no evidence of chemical degradation for insulin either in physical mixture or after tableting during one-year storage at 4\ub0C. Notably, the aqueous coating process seemed not to impact on the peptide stability. Differently from samples stored at 4\ub0C, those kept at 25\ub0C and 60% RH showed an approximately 50% decrease in the drug content, which was even more marked for uncoated cores. Moreover, in vitro release performances, which were characterized by the pursued lag phase followed by a prompt release of insulin, appeared unchanged throughout the whole 4\ub0C storage period. Conclusion. A time-dependent oral insulin delivery system was prepared and evaluated. Neither the manufacturing process nor storage at 4\ub0C for one year showed to impair the drug stability. Delayed release of the model peptide was achieved through the abovedescribed drug delivery platform, thus potentially meeting the requirements of time-based colon targeting

Feasibility, stability and release performance of a time-dependent insulin delivery system intended for oral colon release

The aim of the present work was to evaluate the viability of a time-dependent delivery platform (ChronotopicTM) in preparing an insulin-based system intended for oral colon delivery. The main objectives were to assess the influence of the manufacturing process and storage conditions on the protein stability. Insulin-loaded cores were manufactured by direct compression and subsequently coated with hydroxypropyl methylcellulose (HPMC) in a top-spray fluid bed up to increasing weight gains, namely 20%, 60% and 100%. In order to evaluate the impact operating conditions may have on the protein integrity, insulin and its main degradation products (A21-desamido insulin-A21, Other Insulin Related Compounds-OIRC; High Molecular Weigh Proteins-HMWP) were assayed on samples collected after each process step by chromatographic methods. Furthermore, long-term (4°C) and accelerated (25°C-60% RH) stability studies were carried out on tablet cores and coated systems by assessing insulin, A21, OIRC and HMWP percentages throughout a one-year storage period. In addition, the in vitro release behavior was investigated during the same study period. The overall results indicated that the manufacturing process is not detrimental for insulin integrity and 4°C storage temperature alter neither the protein content nor the release performances of the device. It was therefore concluded that insulin-containing systems intended for oral colon delivery can be obtained by the ChronotopicTM technology