Development and In-Vitro Evaluation of Ethyl Cellulose Micropellets as a Controlled Release Dosage Form for Theophylline

A micropellet dosage form was developed using ethyl cellulose as a polymer with a view to achieve a controlled release oral drug delivery system for theophylline. Drugpolymer ratios and stirring speeds were found to influence the size-distribution of micropellets. Time required for 50% release of theophylline from micropellets was found to vary linearly with the drug content and reciprocal of diameter of micropellets. Invitro release of theophylline from micropellets, having different drug-polymer ratios and different sizes, was found apparently to follow both the First-order release and Diffusion controlled release processes. By differential rate treatment it was found that the overall release, in fact, followed diffusion controlled process.     

Development and In-Vitro Evaluation of Ethyl Cellulose Micropellets as a Controlled Release Dosage Form for Theophylline

Abstract

A micropellet dosage form was developed using ethyl cellulose as a polymer with a view to achieve a controlled release oral drug delivery system for theophylline. Drugpolymer ratios and stirring speeds were found to influence the size-distribution of micropellets. Time required for 50% release of theophylline from micropellets was found to vary linearly with the drug content and reciprocal of diameter of micropellets. Invitro release of theophylline from micropellets, having different drug-polymer ratios and different sizes, was found apparently to follow both the First-order release and Diffusion controlled release processes. By differential rate treatment it was found that the overall release, in fact, followed diffusion controlled process.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Aqueous-Based Cellulose Acetate Butyrate Dispersion: Screening of Process and Formulation Variables to Obtain Verapamil HCl-Controlled Release Beads

The objectives of the present investigation were to evaluate the possibility of using a custom-designed cellulose acetate butyrate (CAB) pseudolatex dispersion on Verapamil HCl-loaded beads for sustained release of the drug. Excipient compatibility was studied by thermal analysis, X-ray diffraction, and content analysis. Inert beads (Nupareil) were loaded with verapamil HCl and subsequently coated with CAB pseudolatex dispersion. Process and formulation factors were screened by Plackett-Burman screening design in order to identify the most important factors affecting the amount of verapamil HCl released in 12 hours. X-ray diffraction pattern and content analysis showed no degradation of verapamil HCl and suggested absence of any interaction. However, thermal analysis indicated an interaction between verapamil HCl and excipient. A polynomial equation was developed to show the relationship between dependent and independent variables. The mathematical model fitted the data and explained 98.05 % of variability in the response. The difference between observed and predicated values of any given run did not exceed 6 % of maximum cumulative release at 12 hours. Plackett-Burman screening design identified coating weight gain, duration of curing, and amount of plasticizer as the most important factors determining cumulative percent released in 12 hours. Amount of Polydextrose/HPMC (Opadry II), spray rate, fluid bed coater outlet temperature, and atomizing pressure had no statistically significant (p < 0.05) influence on the response.     

Release Rate of Drugs from Ethyl Cellulose Coated Granules Containing Caffeine and Salicylic Acid

Fluidized bed coating with ethyl cellulose., polyethylene glycol mixtures has been utilized for prolongation of drug release from granules containing salicylic acid and caffeine as model drugs. Drug release from the coated granules followed first order kinetics.

Particle size of the active material, granule composition and extraction medium pH did not affect the rate and kinetics of drug release. Increase in coat thickness decreased the release rate whereas elevation of the ratio of polyethylene glycol to ethyl cellulose enhanced the release rate to a degree related to the polyethylene glycol concentration. The permeability constants of salicylic acid and caffeine for the ethyl cellulose-polyethylene glycol coatings were of a similar order to those measured previously using solutions of the drugs with planar barrier films.     

Release Rate of Drugs from Ethyl Cellulose Coated Granules Containing Caffeine and Salicylic Acid

Abstract

Fluidized bed coating with ethyl cellulose., polyethylene glycol mixtures has been utilized for prolongation of drug release from granules containing salicylic acid and caffeine as model drugs. Drug release from the coated granules followed first order kinetics.

Particle size of the active material, granule composition and extraction medium pH did not affect the rate and kinetics of drug release. Increase in coat thickness decreased the release rate whereas elevation of the ratio of polyethylene glycol to ethyl cellulose enhanced the release rate to a degree related to the polyethylene glycol concentration. The permeability constants of salicylic acid and caffeine for the ethyl cellulose-polyethylene glycol coatings were of a similar order to those measured previously using solutions of the drugs with planar barrier films.     

Effect of Formulation Components on Drug Release from Multiparticulates

Abstract

The effect of excipients on the release of drug from multiparticulates or pellets coated and uncoated prepared by the extrusion/spheronization and centrifugal processes is reviewed in this paper. A processing viewpoint has been taken because of the relationship between a rugged scaleable process and reliable excipients. Only aqueous coating dispersions have been reviewed because of their increasing usage due to environmental and cost reduction programs.     

Effect of Formulation Components on Drug Release from Multiparticulates

The effect of excipients on the release of drug from multiparticulates or pellets coated and uncoated prepared by the extrusion/spheronization and centrifugal processes is reviewed in this paper. A processing viewpoint has been taken because of the relationship between a rugged scaleable process and reliable excipients. Only aqueous coating dispersions have been reviewed because of their increasing usage due to environmental and cost reduction programs.     

The Effect of Bases and Formulation on the Release of Indomethacin from Suppositories

The in vitro release characteristics of indomethacin from different suppository formulations were investigated using a dialysis method. Suppositories containing 100 mg of indomethacin were prepared by the fusion method in a variety of Witepsol and Novata bases with different hydroxyl values. The rate of release of indomethacin was found to be unexpectedly higher from oily bases with low hydroxyl values.

Furthermore, the effect of surface active agents and some excipients commonly used in suppository formulations on the release properties of indomethacin was determined. Colloidal silicon dioxide, sodium lauryl sulphate and cetyl alcohol had a slight effect, on the release of indomethacin, whereas dioctyl sodium sulphosuccinate significantly increased the amount of indomethacin released. White beeswax and Tween-80, however, resulted in a marked decrease in the release of indomethacin.

The in vitro release of indomethacin from five commercially available preparations was also determined using the same method. Suppositories formulated in PEG bases gave better release properties than those in oily bases.     

The Effect of Bases and Formulation on the Release of Indomethacin from Suppositories

The in vitro release characteristics of indomethacin from different suppository formulations were investigated using a dialysis method. Suppositories containing 100 mg of indomethacin were prepared by the fusion method in a variety of Witepsol and Novata bases with different hydroxyl values. The rate of release of indomethacin was found to be unexpectedly higher from oily bases with low hydroxyl values.

Furthermore, the effect of surface active agents and some excipients commonly used in suppository formulations on the release properties of indomethacin was determined. Colloidal silicon dioxide, sodium lauryl sulphate and cetyl alcohol had a slight effect, on the release of indomethacin, whereas dioctyl sodium sulphosuccinate significantly increased the amount of indomethacin released. White beeswax and Tween-80, however, resulted in a marked decrease in the release of indomethacin.

The in vitro release of indomethacin from five commercially available preparations was also determined using the same method. Suppositories formulated in PEG bases gave better release properties than those in oily bases.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Abstract

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

乙基纤维素接枝L-丙交酯共聚物的制备、表征及其热性能

在辛酸亚锡催化下,成功制备了乙基纤维素与聚L-乳酸接枝共聚物。产物经GPC、FTIR、1HNMR、13CNMR表征,证实L-丙交酯在乙基纤维素残存的羟基上发生开环聚合,接枝到乙基纤维素骨架上。研究了丙交酯纯度、投料比、催化剂用量、反应时间、反应温度对接枝率的影响,并利用DSC和TG研究了接枝物的热性能。     

Effect of Process Variables on Drug Release from Microparticles Containing A Drug-Resin Complex

Abstract

Microparticles consisting of dextromethorphan-resin complex (resinate) coated with a cellulose derivative were prepared by a modified emulsion-solvent evaporation method. Adjustment of the release rate was achieved by varying resinate (core) to polymer (coat) ratio or by using additives. Higher ratios of resinate to polymer gave faster release of the drug. Polyethylene glycol (PEG) 4000 also increased the release rate. Increasing core to coat ratio also increased average particle size. Placing the emulsifying agent in different phases of the emulsion in the fabrication process also affected the particle size distribution. The microparticles showed good sustained release of the drug     

Effect of Microsphere Size and Formulation Factors on Drug Release from Controlled-Release Furosemide Microspheres

Controlled-release furosemide microspheres were prepared with various combinations of Eudragit L: Eudragit RS and Eudragit S: Eudragit RS and release of drug from microspheres containing these polymers in different ratios was studied. A wide range of release rates of drug can obtained by a simple change in the ratio of polymers. An increase in Eudragit RS content of polymer microsphere matrix brought about a decrease in the release rate.

On the other hand, the effect of particle size on the drug release rate from furosemide microspheres was also investigated. The effect of microsphere sizes on release rate depends on the type of Eudragit. The decrease in release rates of small microspheres may be due to agglomerate formation. Dissolution data indicated that the release followed Higuchi's matrix model kinetics.     

Michoencapsulation and in Vitro Dissolution of Oxazepam from Ethyl Cellulose Microcapsules

Microcapsules of oxazepam with core:wall ratios 1:1 and 1:2 have been prepared by coacervation-phase separation method, using ethyl cellulose as a coating material. Phase separation was obtained by adding a salt solution to the dispersion of a water insoluble material in organic solution. Mioroencapsulation process protected oxazepam from photochemical decomposition and retarded its release. Release of the drug into simulated gastric and intestinal juice was studied. In vitro dissolution studies showed that first order release characteristics were exhibited.     

Michoencapsulation and in Vitro Dissolution of Oxazepam from Ethyl Cellulose Microcapsules

Abstract

Microcapsules of oxazepam with core:wall ratios 1:1 and 1:2 have been prepared by coacervation-phase separation method, using ethyl cellulose as a coating material. Phase separation was obtained by adding a salt solution to the dispersion of a water insoluble material in organic solution. Mioroencapsulation process protected oxazepam from photochemical decomposition and retarded its release. Release of the drug into simulated gastric and intestinal juice was studied. In vitro dissolution studies showed that first order release characteristics were exhibited.     

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6000 (PEG 6000), and hydroxyethyl-cellulose (HEC) as possible alternatives to the use of HPMC to control the release of caffeine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most effective for the release of caffeine from the core-in-cup compressed tablets, and that PEG 6000 was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.     

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

Abstract

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6000 (PEG 6000), and hydroxyethyl-cellulose (HEC) as possible alternatives to the use of HPMC to control the release of caffeine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most effective for the release of caffeine from the core-in-cup compressed tablets, and that PEG 6000 was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.