Osmotic Pressure Of Dissolution Medium Research Articles

Formulation and Optimization of Porous Osmotic Pump based Controlled release System of Ritonavir for the Treatment of HIV Infection

The current research involves the development of controlled porosity osmotic pump (CPOP) tablets of ritonavir for the treatment of HIV infection. Core tablets were prepared by wet granulation method using hydroxyl propyl methyl cellulose (HPMCE5LV) polymer, mannitol as osmogen, MCC as diluents and other additives. The CPOP tablets were coated with cellulose acetate as wall forming material, poly ethylene glycol as flux regulating agent, and sorbitol acts as pore forming material in SPM. The prepared tablets were evaluated for FTIR, DSC, pre compression parameters, post compression parameters, in vitro drug release study and scanning electron microscopy study. The optimized formulation RM5 showed 94.83% at the end of 14 hrs with zero order drug release. The difference factor (f1) and similarity factor (f2) for RM5 were observed 14.61 and 75.12 respectively. Optimized formulation did not show any significant change on the pH and agitation intensity, but it depends on osmotic pressure of dissolution media indicated that mechanism of drug release was due to osmotic pressure. SEM micrographs confirmed that no pores were found before dissolution and after dissolution had shown the porous nature of the membrane. Short term stability study at 40±2oC/75±5% RH for three months on the RM5 formulation indicated that there was no significant change weight variation, % friability, drug content and in vitro drug release.

FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC PUMP TABLETS FOR ZIDOVUDINE AND LAMIVUDINE COMBINATION USING FRUCTOSE AS OSMOGEN

The present study deals with the development and evaluation of controlled porosity osmotic pump (CPOP) tablets of zidovudine-lamivudine. Wet granulation method was used for the development of core tablets. Core tablets were incorporated with HPMCE5 LV polymer, different concentrations of fructose as osmogen and additives. The CPOP tablets were coated with cellulose acetate as a wall forming material, polyethylene glycol as flux regulating agent, and sorbitol acts as pore forming material in SPM. The formulated tablets were evaluated for FTIR, DSC, pre-compression parameters, post compression parameters, in vitro drug release study and scanning electron microscopy study. The optimized formulation had no significant effect on the p H and agitation intensity, but depends on the osmotic pressure of dissolution media indicated that mechanism of drug release. SEM images revealed that no pores were found before dissolution and after dissolution had shown the porous nature of the membrane. Short term stability study at 40±2oC /75±5% RH for the months on the CF4 formulation indicated that there was no significant change weight variation, % friability, drug content and in vitro drug release. Keywords: HPMCE5LV, wet granulation, CPOP, in vitro drug release, stability study .

Controlled porosity solubility modulated osmotic pump tablets of gliclazide.

A system that can deliver drug at a controlled rate is very important for the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Poorly water-soluble drug with pH-dependent solubility such as gliclazide (GLZ) offers challenges in the controlled-release formulation because of low dissolution rate and poor bioavailability. Solid dispersion (SD) of GLZ consisted of hydroxypropyl cellulose (HPC-SSL) as a polymeric solubilizer was manufactured by hot melt extrusion (HME) technology. Then, controlled porosity osmotic pump (CPOP) tablet of gliclazide was designed to deliver drug in a controlled manner up to 16h. The developed formulation was optimized for type and level of pore former and coating weight gain. The optimized formulation was found to exhibit zero order kinetics independent of pH and agitation speed but depends on osmotic pressure of dissolution media indicated that mechanism of drug release was osmotic pressure. The in vivo performance prediction of developed formulation using convolution approach revealed that the developed formulation was superior to the existing marketed extended-release formulation in terms of attaining steady state plasma levels and indicated adequate exposure in translating hypoglycemic response. The prototype solubilization method combined with controlled porosity osmotic pump based technique could provide a unique way to increase dissolution rate and bioavailability of many poorly water-soluble, narrow therapeutic index drugs used in diabetes, cardiovascular diseases, etc.

Development and Optimization of Osmotically Controlled Asymmetric Membrane Capsules for Delivery of Solid Dispersion of Lycopene

The aim of the present investigation is to develop and statistically optimize the osmotically controlled asymmetric membrane capsules of solid dispersion of lycopene. Solid dispersions of lycopene with β-cyclodextrin in different ratios were prepared using solvent evaporation method. Solubility studies showed that the solid dispersion with 1 : 5 (lycopene : β-cyclodextrin) exhibited optimum solubility (56.25 mg/mL) for osmotic controlled delivery. Asymmetric membrane capsules (AMCs) were prepared on glass mold pins via dip coating method. Membrane characterization by scanning electron microscopy showed inner porous region and outer dense region. Central composite design response surface methodology was applied for the optimization of AMCs. The independent variables were ethyl cellulose (X 1), glycerol (X 2), and NaCl (X 3) which were varied at different levels to analyze the effect on dependent variables (percentage of cumulative drug release (Y 1) and correlation coefficient of drug release (Y 2)). The effect of independent variables on the response was significantly influential. The F18 was selected as optimized formulation based on percentage of CDR (cumulative drug release) of 85.63% and correlation coefficient of 0.9994. The optimized formulation was subjected to analyze the effect of osmotic pressure and agitational intensity on percentage of CDR. The drug release was independent of agitational intensity but was dependent on osmotic pressure of dissolution medium.

Experiment on formulation and drug release behavior of porosity asymmetric membrane capsules in vitro

Porosity asymmetric membrane capsules were prepared to study the relationship between the capsule formulation and drug release. Cellulose acetate (CA) and pore formers were used in the capsule shell formulation as the main semipermeable membrane material. The capsules were permeable to both water and dissolved solutes. Using sparingly soluble drug acetaminophen as a model, cumulative release was calculated. The slope of the release profile from the distilled water had good relationship with the concentration of the pore formers F68. The release of acetaminophen was independent to the pH, osmotic pressure of dissolution medium, but influenced by intensity of agitation. When the concentration of pore former was low, zero-order release behavior was observed within 24 h which was consistent with Fickian diffusion model. When the concentration of pore former was high, however, Higuchi model release was found which is caused by Fickian diffusion and osmotic pressure release. With scanning electron microscope (SEM), the surface structure and cross-section of the capsule shell were also studied before and after drug delivery. With simple preparation and broad scope of drug application, porosity asymmetric membrane capsules can give desired drug extended release and show more convenience than controlled tablets with laser drilling.

Push-pull osmotic pump for zero order delivery of lithium carbonate: Development and in vitro characterization

Lithium carbonate, a drug with narrow therapeutic index, needs therapeutic drug monitoring and dose adjustment to maintain lithium level within the therapeutic window. Conventional formulations of lithium carbonate exhibit immediate drug release causing swing/fluctuations in the plasma concentration of lithium, consequently leading to unfavorable side-effects and make dose adjustment difficult. The push-pull osmotic pump has been developed for zero order delivery of lithium carbonate for a period of 24 h. The effect of various formulation variables on bilayer core tablet and its semi permeable coating along with orifice diameter have been investigated and optimized for desired drug release profile. Drug release was found to be inversely proportional to the membrane thickness but directly related to the amount of pore formers in the semipermeable membrane. Images from a scanning electron microscope confirmed the presence of pores in the semipermeable membrane which facilitated the required water penetration. No distortion or change in orifice shape was noticed prior to and after the dissolution study. Drug release from the developed formulation was found to be independent of pH, agitation intensity and agitation mode but depended on osmotic pressure of dissolution media.