Thermal sintering: a novel technique used in the design, optimization and biopharmaceutical evaluation of propranolol HCl gastric floating tablets.

The objective of the present investigation was to study the applicability of thermal sintering technique for the development of gastric floating tablets of propranolol HCl. Formulations were prepared using four independent variables, namely (i) polymer quantity, (ii) sodium bicarbonate concentration, (iii) sintering temperature and (iv) sintering time. Floating lag time and t95 were taken as dependent variables. Tablets were prepared by the direct compression method and were evaluated for physicochemical properties, in vitro buoyancy and dissolution studies. From the drug release studies, it was observed that drug retarding property mainly depends upon the sintering temperature and time of exposure. The statistically optimized formulation (PTSso) was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies, and no significant chemical interaction between drug and polymer was observed. Optimized formulation was stable at accelerated conditions for a period of six months. PTSso was evaluated for in vivo buoyancy studies in humans for both fed and fasted states and found that gastric residence time of the floating tablets were enhanced by fed stage but not in fasted state. Optimized formulation PTSso and commercial formulation Ciplar LA 80 were subjected to bioavailability studies in healthy human volunteers by estimating pharmacokinetic parameters such as Cmax, Tmax, area under curve (AUC), elimination rate constant (Kel), biological half-life (t1/2) and mean residence time (MRT). There was a significant increase in the bioavailability of the propranolol HCl from PTSso formulation, which was evident from increased AUC levels and larger MRT values than Ciplar LA 80.

An in vitro and in vivo investigation into the suitability of compression coated tablets of indomethacin for the treatment of rheumatoid arthritis which follow circadian rhythms.

OBJECTIVE: The aim of this study was to develop chronotherapeutic drug delivery system of indomethacin using polyethylene oxide (PEO) with a predetermined lag time of 6 h by compression coating technique. MATERIALS AND METHODS: Solid dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was formulated as immediate release core tablet which were further coated with PEO (WSR Coagulant or WSR N12 K) using compression coating technique. Compression coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet weight and coating polymer was considered as optimized formulation, which was further characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transformed infrared spectroscopy, and scanning electron microscopy. RESULTS: The results indicated that there was no chemical incompatibility and slight change in surface properties. C(max), area under the curve (AUC(0-t)), and T(max) following oral ingestion of commercial capsule (Indocap) and optimized formulation (CT 4) were found to be 1973.18 ± 36.89 ng/mL, 11090.09 ± 131.21 ng/mL/h, 0.99 ± 0.02 h and 2115.46 ±6 2.61, 10413.14 ± 299.66 ng/mL/h, 7.00±0.02 h, respectively. CONCLUSION: Unaltered AUC(0-t) and C(max), but delayed T(max) indicated clear lag time before immediate release of drug which is suitable for treating rheumatoid arthritis following circadian rhythm.

Thermal sintering: a novel technique in the design of gastroretentive floating tablets of propranolol HCl and its evaluation.

The aim of the present investigation was to formulate thermally sintered floating tablets of propranolol HCl, and to study the effect of sintering conditions on drug release, as well as their in vitro buoyancy properties. A hydrophilic polymer, polyethylene oxide, was selected as a sintered polymer to retard the drug release. The formulations were prepared by a direct compression method and were evaluated by in vitro dissolution studies. The results showed that sintering temperature and time of exposure greatly influenced the buoyancy, as well as the dissolution properties. As the sintering temperature and time of exposure increased, floating lag time was found to be decreased, total floating time was increased and drug release was retarded. An optimized sintered formulation (sintering temperature 50 degrees C and time of exposure 4 h) was selected, based on their drug retarding properties. The optimized formulation was characterized with FTIR and DSC studies and no interaction was found between the drug and the polymer used.

Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum).

The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12 h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer.

Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl.

Abstract. The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug's gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

Statistical optimization of a novel excipient (CMEC) based gastro retentive floating tablets of propranolol HCl and it's in vivo buoyancy characterization in healthy human volunteers.

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of propranolol HCl by central composite design and to study the effect of formulation variables on floating lag time, D1hr (% drug release at 1 hr) and t90 (time required to release 90% of the drug). 3 factor central composite design was employed for the development of GRFDDS containing novel semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) as a release retarding polymer. CMEC, sodium bicarbonate and Povidone concentrations were included as independent variables. The tablets were prepared by direct compression method and were evaluated for in vitro buoyancy and dissolution studies. From the polynomial model fitting statistical analysis, it was confirmed that the response floating lag time and D1hr is suggested to quadratic model and t90 is suggested to linear model. All the statistical formulations followed first order rate kinetics with non-Fickian diffusion mechanism. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. Statistically optimized formulation was characterized by FTIR and DSC studies and found no interactions between drug and polymer. The results demonstrate the feasibility of the model in the development of GRFDDS containing a propranolol HCl. Statistically optimized formulation was evaluated for in vivo buoyancy studies in healthy humans for both fed and fasted states. From the results, it was concluded that gastric residence time of the floating tablets were enhanced at fed stage but not in fasted state.