Optimization and Development of Swellable Controlled Porosity Osmotic Pump Tablet for Theophylline
ABSTRACT Purpose: To develop swellable controlled porosity osmotic pump tablet of theophylline and to define the formulation and process variables responsible for drug release by applying statistical optimization technique. Methods: Formulations were prepared based on Taguchi Orthogonal Array design and Fraction Factorial design for core and coating, respectively. The tablets were prepared by direct compression and wet granulation methods; spray coated with ethyl cellulose solution containing varying amounts of PEG 400 and plasdone. Drug release from the osmotic drug delivery system was studied using USP Type I paddle type apparatus. The membrane morphology of the delivery system was determined by scanning electron microscopy (SEM). Results: Optimization results indicated that the release rate of theophylline from the swellable controlled porosity osmotic pump tablet is directly proportional to the levels of osmotic agent, solubilizing agent and pore former in the tablet core and the membrane, respectively. SEM showed the formation of pores in the membrane through which drug release occurred. The best formulation showed 98.2 % drug release and complied with USP requirements. Conclusion: The results confirmed that the factors responsible for drug release were osmotic agents (core) and pore former (membrane). Also, the preparation of swellable controlled porosity osmotic pump tablet was facilitated by coating the core tablet with pore forming agent, thus eliminating the need for the more expensive laser drilling.
Full-textDOI: · Available from: Utpal Sanki, May 07, 2015
SourceAvailable from: Jumah Masoud Mohammad Salmani[Show abstract] [Hide abstract]
ABSTRACT: It is difficult to retard the release of highly water soluble drugs due to their fast dissolution and absorption in gastro intestinal tract. A novel methylcellulose based elementary osmotic pump tablets of metoprolol succinate, which was used as a model drug, has been designed to overcome these drawbacks. Taguchi orthogonal L18 array design with analysis of variance was conducted to optimize the release profile. The results showed that the drug release was inversely proportional to the viscosity and amount of methylcellulose, thickness of semipermeable membrane and amount of dibutylphtalate, while it was directly proportional to the amount of polyethylene glycol 400 and independent to the compacting method and orifice size. The results approved also the reliability of this system to control the release of drug at zero order kinetic for up to 12 hours. The in vivo studies conducted in rabbits using the optimized and marketed formulations revealed that in addition to the enhanced bioavailability, this design maintained a constant therapeutic drug concentration within plasma even up to 24h independently to the pH variations, in conclusion this approach can circumvent all intra and inter subject variations in gastric physiology and serve as promising delivery system for highly water soluble drugs. © 2014 Universal Research Publications. All rights reserved KEY WORDS: Elementary osmotic pump, methylcellulose, Taguchi orthogonal design, zero order kinetic..
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ABSTRACT: Purpose: To develop and characterize bilayer tablet formulations of tramadol HCl (TmH) and acetaminophen (AAP) microparticles. Methods: Coacervation via temperature change was the encapsulated method used for the preparation of the microparticles, with ethyl cellulose (EC) of medium viscosity as the polymer for extending drug release. The microparticles of the two drugs were prepared separately and then compressed into bilayer tablets. The physicochemical compatibility and stability of the tablets were determined by Fourier transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) while their mechanism and pattern of drug release were assessed by applying Higuchi, Zero order, First order and Korsmeyer-Peppas kinetic models. Bilayer tablets were subjected to accelerated stability studies for three months. Results: FTIR, XRD, DSC and TGA data for the formulations indicate good compatibility and stability. Furthermore, accelerated stability studies confirmed the stability of the formulations. Controlled drug release from the microparticles and bilayer tablets was observed for 8 h and 12 h, respectively. The Higuchi model produced the best fit, with regard to release profile, for both drugs, with correlation coefficient (R 2) of 0.966 and 0.960 for AAP and TmH, respectively. Conclusion: Microencapsulated TmH and AAP can be developed into suitable bilayer tablets that are stable and capable of releasing the drugs over 12 h.Tropical Journal of Pharmaceutical Research 09/2010; 9(9):347-348. DOI:10.4314/tjpr.v9i4.58926 · 0.50 Impact Factor
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ABSTRACT: The osmotic drug delivery systems suitable for oral administration typically consist of a compressed tablet core that is coated with a semipermeable membrane that has an orifice drilled on it by means of a laser beam or mechanical drill. Ketorolac is a nonsteroidal agent with powerful analgesic. Oral bioavailability of ketorolac was reported to be 90% with very low hepatic first-pass elimination; the biological half-life of 4-6 hours requires frequent administration to maintain the therapeutic effect. The aim of the current study was to design a controlled porosity osmotic pump (CPOP)based drug delivery system for controlled release of an NSAID agent, ketorolac tromethamine, which is expected to improve patient compliance due to reduced frequency; it also eliminates the need for complicated and expensive laser drilling and maintain continuous therapeutic concentration. The CPOP was designed containing pore-forming water-soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a micro porous structure. The effect of different formulation variables, namely level of pore former (PVP), plasticizer (dibutyl phthalate) in the membrane, and membrane weight gain were studied. Drug release was inversely proportional to the membrane weight but directly related to the initial concentration of pore former (PVP) in the membrane. Drug release was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Based on the in vitro dissolution profile, formulation F3C1 (containing 0.5 g PVP and 1 g dibutyl phthalate in coating membrane) exhibited Peppas kinetic with Fickian diffusion-controlled release mechanism with a drug release of 93.67% in 12 hours and hence it was selected as optimized formulation. SEM studies showed the formation of pores in the membrane. The formulations were stable after 3 months of accelerated stability studies. CPOP was designed for effective administration of drugs for prolonged period of time.12/2012; 4(1):2-9. DOI:10.4103/0976-0105.109398