Effect of Drug (Core) Particle Size on the Dissolution of Theophylline from Microspheres Made from Low Molecular Weight Cellulose Acetate Propionate (original) (raw)
Related papers
2011
Purpose: To formulate theophylline microspheres with cellulose acetate using solvent evaporation method and evaluate the effect of various processing factors on their characteristics. Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer- cellulose acetate- by an emulsion solvent evaporation technique using an acetone/liquid paraffin system containing Span 80 as a surfactant. The effect of processing factors, e.g., varying drug/polymer ratio (1:1, 1:2, 1:3) and temperature (10 and 35 °C) on microsphere characteristics and drug release were examined. Similarly, microspheres with a drug/polymer ratio of 1:3 incorporating Span 20 were also also prepared and evaluated. Results: The microspheres were white, free-flowing and spherical. The yield varied from 73.0 to 87.5 % while entrapment efficiency was in the region of 71.8 to 92.4 %. High drug/polymer ratio, Span 80 (surfactant) and processing temperature between 10 and 30 °C produced form...
Tropical Journal of Pharmaceutical Research, 2011
Purpose: To formulate theophylline microspheres with cellulose acetate using solvent evaporation method and evaluate the effect of various processing factors on their characteristics. Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer-cellulose acetate-by an emulsion solvent evaporation technique using an acetone/liquid paraffin system containing Span 80 as a surfactant. The effect of processing factors, e.g., varying drug/polymer ratio (1:1, 1:2, 1:3) and temperature (10 and 35 °C) on microsphere characteristics and drug release were examined. Similarly, microspheres with a drug/polymer ratio of 1:3 incorporating Span 20 were also also prepared and evaluated. Results: The microspheres were white, free-flowing and spherical. The yield varied from 73.0 to 87.5 % while entrapment efficiency was in the region of 71.8 to 92.4 %. High drug/polymer ratio, Span 80 (surfactant) and processing temperature between 10 and 30 °C produced formulations with better drug entrapment efficiency. High drug/polymer ratio, low processing temperature and low HLB value of surfactant enhanced the sustained drug release characteristics of the microspheres. Conclusion: The combination of three suitable factors-Span mixture (with HLB value of 4.3), processing temperature of 10 °C and drug/polymer ratio of 1:3-produced a suitable controlled release theophilline microsphere formulation which could be effective for the management of asthma.
PubMed, 2010
The objective of the present investigation was to design a sustained release floating microcapsules of theophylline using two polymers of different permeability characteristics; Eudragit RL 100 (Eu RL) and cellulose acetate butyrate (CAB) using the oil-in-oil emulsion solvent evaporation method. Polymers were used separately and in combination to prepare different microcapsules. The effect of drug-polymer interaction was studied for each of the polymers and for their combination. Encapsulation efficiency, the yield, particle size, floating capability, morphology of microspheres, powder X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC) were evaluated. The in vitro release studies were performed in PH 1.2 and 7.4. The optimized drug to polymer ratios was found to be 4:1 (F(2)) and 0.75:1 (F'(2)) with Eu RL and CAB, respectively. The best drug to polymer ratio in mix formulation was 4:1:1 (theophylline: Eu RL: CAB ratio). Production yield, loading efficiencies, and particle size of F(2) and F'(2) were found to be 59.14% and 45.39%, 73.93% and 95.87%, 372 and 273 micron, respectively. Microsphere prepared with CAB showed the best floating ability (80.3 ± 4.02% buoyancy) in 0.1 M HCl for over 12 h. The XRD and DSC showed that theophylline in the drug loaded microspheres was stable and in crystaline form. Microparticles prepared using blend of Eu RL and CAB polymers indicated more sustained pattern than the commercial tablet (P<0.05). Drug loaded floating microballoons prepared of combination of Eu RL and CAB with 1:1 ratio were found to be a suitable delivery system for sustained release delivery of theophylline which contained lower amount of polymer contents in the microspheres.
Indian Journal of Pharmaceutical Sciences, 2006
Oral dosage forms containing 300 mg theophylline in matrix-type tablets were prepared by direct compression method using two kinds of matrices-glycerylbehenate (hydrophobic) and hydroxypropylmethyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations-the zero-order equation, the first-order equation, the Higuchi square root equation, and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first-order kinetics, and the release process involves erosion/ diffusion and an alteration in the surface area and diameter of the matrix system as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and Hixson-Crowell cube root law.
Pharmaceutical Development and Technology, 2011
Altering the combined hydrophilic-lipophilic balance (CHLB), by varying the ratio of dual surfactants, on formulation parameters and in vitro drug release of ethyl cellulose microspheres was examined. Theophylline, a xanthine bronchodilator was used to model controlled release owing to its narrow therapeutic index. Microspheres were prepared using different ratios of dual surfactant in an emulsion-solvent evaporation process. Drug loading, encapsulation efficiency, particle size distribution, and geometric mean diameters were evaluated. Drug release was evaluated using several kinetic models including zero and first order, Higuchi square root, and Hixson-Crowell. Microspheres presented as mostly spherical particles and diffusional drug release was affected by microsphere construction. For this novel, dual surfactant system the microsphere matrix is a hydrophobic polymer and the release rate may be modulated with variation in ratio of dual surfactants. Dissolution data followed the Higuchi model and supports the formation of a monolithic microsphere matrix that releases theophylline by Fickian diffusion. Dual surfactants for preparation of microspheres are an inadequately studied research area that offers another means to modulate particle size and drug release. For the current study microspheres prepared with surfactant ratios of Span 65: Tween 40 between 3:1 and 2:1 provided the best control of size and drug release.
Jordan Journal of Pharmaceutical Sciences, 2011
The objective of this study was to prepare and evaluate microparticles of Eudragit and Ethyl cellulose binary blend loaded with theophylline for controlled release. Microparticles were prepared by Phase separation method. The method is quite simple, rapid, and economical and does not imply the use of toxic organic solvents. Solid, discrete, reproducible free flowing microparticles were obtained. The yield of the microparticles was up to 92%. More than 85% of the isolated microparticles were of particle size range of 325 to 455 µm. The obtained angle of repose, % carr's index and tapped density values were well within the limits, indicating that prepared microparticles had smooth surface, free flowing and good packing properties. Scanning Electron Microscopy photographs and calculated sphericity factor confirms that the prepared formulations are spherical in nature. Prepared microparticles were sTab. and compatible, as confirmed by DSC and FT-IR studies. The prepared formulations were quantitatively analyzed for the amount of encapsulated drug. It was observed that there is no significant release of the drug at gastric pH. The drug release was controlled more than 12 h. Intestinal drug release from microparticles was studied and compared with the release behavior of commercially available oral formulation Duralyn CR 400. The release kinetics followed different transport mechanisms.
Comparative Evaluation of Theophylline Microsphere prepared using Various Biodegradable Polymers
international journal of chemical sciences, 2008
The present investigation was to formulate theophylline loaded microspheres using different grade of chitosan, chitosan-sodium alginate and chitosan-albumin by the following methods such as phase separation emulsification, modified ionotropic gelation and heat stabilization method. The prepared microspheres were evaluated in terms of drug content, incorporation efficiency, micromeritic studies, moisture content and in vitro drug release profile. Chitosan-sodium alginate combination produced microspheres with spherical, smooth surface and frees flowing. It exhibited incorporation efficiency above 75% and size range between 999-994 µm. The drug release from the microspheres follows first order kinetics and the mechanism is Higguchi's diffusion. Theophylline loaded microspheres prepared from Chitosan-sodium alginate combination exhibited good sustained release characteristics and was found suitable for chronic obstructive pulmonary disease (COPD) and nocturnal asthma.
Preparation and in vitro evaluation of a microballoon delivery system for theophylline
2010
A multiple-unit oral floating system was prepared using the emulsification-solvent diffusion method to prolong the gastric emptying time of theophylline. For this purpose, theophylline, ethyl cellulose and dibutyl phthalate were dissolved in an ethanol/dichloromethane mixture, added to 0.1 M HCl containing NaCl (20%) or saturated theophylline and/or different concentrations of polysorbate 80 and polyvinyl alcohol. The mixture was stirred at different speeds for 3 h. The resulting microspheres were separated from the solution by filtration. Physical characteristics, including the shape and size distribution, floating capability, drug loading and drug release of the resulting theophylline microspheres were investigated. The prepared microspheres tended to float over the simulated gastric medium for over 12 h. Addition of NaCl (20%) to the aqueous phase increased the drug loading of microballoons. The mean geometric diameter of microspheres decreased, as the stirring speed rate or the polysorbate 80 concentration were increased. Microballoons prepared at higher stirring rates released their drug content faster. Also, it is concluded that particle size and floating capability of microballoons could be adjusted by altering the stirring rate during microencapsulation.
Brazilian Journal of Pharmaceutical Sciences, 2016
The present study describes the development of theophylline microcapsules by a non-solvent addition method and the effect of plasticizer addition on microencapsulation. The release was studied in distilled water and the data were analysed by various mathematical models for determining the mechanism of release. Prepared microcapsules were found to be spherical, free flowing and having more than 80% entrapped drug. The polymer - cellulose acetate phthalate and plasticizer - polyethylene glycol was considered to be affecting the properties of microcapsules including drug release (time for 50% drug release, T50). The formulation with the highest proportion of polymer and without plasticizer (F3) showed the slowest release with T50 = 4.3 h, while the formulation with lower proportion of polymer and 20% (w/w) plasticizer (F13 &14) showed the fastest release of drug with T50 values of 1.2 h and 1.3 h, respectively. The drug release from most of the formulations was found to be following Hi...
IN VITRO DISSOLUTION KINETIC STUDY OF THEOPHYLLINE FROM HYDROPHILIC AND HYDROPHOBIC MATRICES
Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.