In Vitro Dissolution Profile of Theophvlline Lorded Ethvl Cellulose Microspheres Preprred by Emulsificrtion Soluent Eurporrtion

Theophylline was entrapped in ethyl cellulose microspheres by a water/oil/water emulsification-solvent evaporation method. Aqueous solution of drug was emulsified into a solution of ethyl cellulose in toluene, containing polyisobutylene as protective colloid, followed by emulsification of this primary emulsion into an external aqueous phase to form a water/oil/water emulsion. Microspheres was formed after solvent evaporation and precipitation of ethyl cellulose. In vitro dissolution profile and effect of polyisobutylene on it were studied.     

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.     

In Vitro Release of Neomycin Sulfate from Polymeric Films

Abstract

A study was made of the release of neomycin sulfate from films containing ethyl cellulose or a polyamide. These films were plasticized using hexadecyl alcohol and/or tributyl citrate. Neomycin sulfate was incorporated into the film, and the release of neomycin in a desorbing media of distilled water was measured by periodically removing a sample of desorbing media and determining the neomycin sulfate content spectrophotometrically. The release of neomycin sulfate from these films was also determined microbiologically. This was carried out by measuring the zone of inhibition surrounding a circular disc containing neomycin sulfate which had been placed onto the surface of a Petri dish containing suitable media inoculated with Bacillus subtilis. Hexadecyl alcohol was noted to suppress or decrease the release of neomycin sulfate from ethyl cellulose and polyamide films. Release of neoraycin sulfate from films of ethyl cellulose plasticized with tributyl citrate showed an increase. The results of the microbiological determination were similar to the spectro-photometric results and indicated that the release of neomycin sulfate from ethyl cellulose/tributyl citrate systems was time dependent.     

In Vitro-In Vivo Correlation of Indomethacin Release from Prolonged Release W/O/W Multiple Emulsion System

Abstract

A prolonged release oral w/o/w multiple emulsion was formulated using hydroxypropyl methyl cellulose as thickening agent. The polymer when used in different proportions, controlled indomethacin release from the biphasic emulsion system. Double emulsification technique was used for formulation of the biphasic emulsion system. The stability of the emulsion was found to be inversely proportional to the drug release characteristics. The in vitro release of indomethacin followed diffusional path through the oil layer and through the polymeric oil. The in vivo release studies were carried out using rabbits as animal models. A good linear correlation was obtained between in vivo-in vitro drug release from such multiple emulsion system.     

Control of Drug Release Rate by Use of Mixtures of Polycaprolactone and Cellulose Acetate Butyrate Polymers

Abstract

Chlorpromazine microspheres were prepared by an emulsion solvent evaporation technique using polycaprolactone and cellulose acetate butyrate as the matrix. The fluidity of the polymer solution was easily adjusted by use of mixtures of two polymers and thus provided a practical means to control the microsphere size. The In Vitro release pattern was easily changed by changing the ratios of these two polymers. An increase in polycaprolactone content of the polymer microsphere matrix brought about an increase in the release rate. Drug loading had no predictable effect on the dissolution rate, but smaller microspheres gave more rapid drug release due to the greater surface area.     

Adsorption of Some 1. 4-Benzodiazepines on Insoluble Tablet Excipients and Charcoal

Abstract

The adsorption of five widely used 1. 4-benzodiazepines on talc, calcium phosphate, magnesium stearate, microcrystalline celluloses, ethyl cellulose and starch was studied. Adsorption of these compounds on charcoal was also investigated for comparison. Diazepam was found not to be adsorbed on talc, calcium phosphate and magnesium stearate. A relatively low adsorption of the drug by cellulose and starch was measured. The amount of diazepam adsorbed per unit weight of ethyl cellulose was high in water and in phosphate buffer, while no adsorption could be measured in 0.1 N HCL. The drug interact with ethyl cellulose at higher concentrations (100-180 mcg/ml). The UV and IR of the reactants and products were studied.

The adsorption of nordiazepam, nitrazepam, flunitrazepam and chlordiazepoxide onto ethyl cellulose and charcoal from their aqueous solutions was also studied. Diazepam and nordiazepam showed the highest adsorption on ethyl cellulose. The desorption of benzodiazepines from ethyl cellulose in 0.1 N HC1 was at the following decreasing rate: flunitrazepam, chlordiazepoxide, nitrazepam, diazepam, nordiazepam.     

Consideration on the Formulation of Benzoyl Peroxide at Ambient Temperature: Choice of Non-Polar Solvent and Preparation of Submicron Emulsion Gels

ABSTRACT

The aim of this study performed at ambient temperature was first to determine the solubility of benzoyl peroxide in various solvents with a large range of polarity. All these solvents can be used in the dermatological field. Then, using the most suitable solvent, a new drug vehicle submicron oil-in-water emulsion was formulated. Correlation between dielectric constant (ε) and drug solubility in various solvents and different binary mixtures was verified. An original ternary diagram with surfactant–co-surfactant/oil/water was performed at low temperature to determine the regions of submicron emulsions. A dramatic change in the magnitude of benzoyl peroxide solubility occurred above a dielectric constant value of about 20. The solubility of this drug can be enhanced by the replacement of polar solvent by a vehicle of lower dielectric constant. A stable submicron emulsion gel was made with cremophor EL, glycerol, caprilic–capric triglycerides, and water in the proportion of 20–20/35/25, respectively; 1.5% benzoyl peroxide was also added. This submicron emulsion vehicle consisted of oil droplets, with a mean diameter of approximately 100–150 nm, dispersed in a continuous water phase. These studies confirm the potential of benzoyl peroxide incorporation into submicron emulsion gel and the stability of this formulation.     

Development and In Vitro Characterization of Chitosan-based Microspheres for Nasal Delivery of Promethazine

ABSTRACT

Conventional and composed promethazine-loaded microspheres were prepared by spray drying of chitosan solution systems and double water-in-oil-in-water (W/O/W) emulsion systems, respectively. Double emulsions were prepared in two different feed concentrations, with chitosan dissolved in both water phases, and ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the microspheres depended on the chitosan content, type and the feed concentration of spray-dried system. Results obtained suggested that better ethylcellulose microcapsules with promethazine in the chitosan matrix were formed when less concentrated emulsion systems were spray-dried. Thus, in case of such a system, with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release was obtained.     

Prolonged Release of Tegafur from S/O/W Multiple Emulsion

Abstract

To develop a prolonged and sustained release preparation, we prepared an albumin microsphere-in-oil-in-water emulsion (S/O/W) and examined sustained release from it in comparison with other control preparations such as water-in-oil (W/O) emulsions and microspheres in vitro and in vivo, respectively. Tegafur was used as a model drug. A microsphere-in-oil emulsion was prepared by adding albumin microspheres to soybean oil containing 20% Span 80. To prepare an S/O/W emulsion, the microsphere-in-oil emulsion was added into an aqueous solution of hydroxypropyl methylcellulose containing Pluronic F68. The mean particle size of the albumin microspheres was 3 µm, and the ratio of entrapment of tegafur into albumin microspheres was about 25%. In an in vitro release test, the t₇₅ of the S/O/W emulsion was fourfold greater and in an in vivo release test the mean residence time of tegafur from the S/O/W emulsion was more than twofold that from a W/O emulsion or microsphere system. The mean residence time of 5-fluorouracil (5-FU) from an S/O/W emulsion was also greater than with other dosage forms. These results suggest the possible usefulness of an S/O/W emulsion for the sustained and prolonged release of tegafur.     

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     

Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Abstract

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

PARTICLE COUNTING OIL AND WATER EMULSIONS

ABSTRACT

Because of their speed and convenience, optical particle counters are widely used for particle size analysis of liquid samples. In some cases, both solid particles and emulsified water or oil may be present in a sample. Since emulsion droplets are counted as if they are solid particles, analysis and data interpretation for these samples are difficult. Until recently, no suitable method existed for distinguishing solid contaminants from emulsion droplets. This paper discusses a method which overcomes this limitation. Through the use of a surfactant-laden nonpolar dilution fluid, water is incorporated into reverse micelles too small to be seen by most optical particle counters. As a result, only solid contaminants are counted, and many problems associated with the analysis of emulsions are overcome. Results obtained from a wide range of oil and water emulsions are used to evaluate the merits and possible applications of the new technique.     

Some Properties of an Ethoxylated Castor Oil and Ethoxylated Oleyl Alcohol

Abstract

Ethoxylated derivates have been used as surfactants for some years. In this work, ethoxylated castor oil and ethoxylated oleyl alcohol alone and/or their I:I mixtures were used as surfactants in oil/water type of emulsion systems.

The physicochemical properties of ethoxylated castor oil (Simulsol OL 50) and ethoxylated oleyl alcohol (Simulsol 98) have been investigated.

Both of these materials have properties associated with non-ionic surfactants, although considerably soluble in water, the compounds have slight solubility in nonpolar solvents.

Surface tensions of aqueous solutions were measured over a temperature range of 20°C to 40°C. CMC were determined by surface tension measurements. pH, refractive index, conductivity and density of the two surfactants were also determined.     

Fabrication of Multiunit Controlled-Release Phenylpropanolamine Hydrochloride Tablets

Abstract

Phenylpropanolamine hydrochloride (PPA) pellets were prepared in a fluidized-bed rotary granulator. Microcrystalline cellulose and distilled water were used as pelletization enhancer and binder, respectively. The pellets were coated with methacry-late ester copolymer (Eudragit® RS 100) solution containing a 1:1 ratio mixture of triethyl citrate and castor oil as plasticizers. The addition of approximately 30% microcrystalline cellulose and 2% croscarmellose sodium to the 50% coated pellets produced fast disintegrating tablets. Dissolution profiles of both pellets and their respective matrix tablets were comparable and conformed to the USP dissolution requirement for PPA extended-release capsules.     

Preparation of ethyl cellulose pseudolatex and studies on suitability of it as a binder for granulation

Ethyl cellulose pseudolatices were prepared by an emulsion-solvent evaporation technique, which consisted of dissolving the polymer in a blend of benzene and ethyl alcohol, followed by the addition of adjuvants. The organic, solvents were removed from the emulsion using vacuum distillation. Physical evaluation of the dispersions and the cast films was carried out.

On the basis of characteristics of cast films selected formulations were fused as granulating agents for preparing chlorpheniramine maleate tablets. Good correlation was observed between total solid in the granulating dispersion and the drug release. The possible mechanisms for the drug release from the tablets are suggested.     

Preparation and Characterization of a Submicron Lipid Emulsion of Docetaxel: Submicron Lipid Emulsion of Docetaxel

Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility, thus Tween 80 and ethanol need to be added into its formulation, probably resulting in the toxic effects. In this study, we aimed to utilize submicron lipid emulsions as a carrier of docetaxel to avoid these potential toxic vehicles. Preformulation study was performed for rational emulsions formulation design, including drug solubility, distribution between oil and water, and degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was prepared by temperature elevation method. Soya oil and Miglyol 812 can incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel, with particle size in the nanometer range, entrapment efficiency more than 90%, and is physicochemically stable at 4 and 25°C for 6 months. Animal studies showed that docetaxel emulsion has significantly higher area under the curve (AUC) and C_max in rats compared to its micellar solution. The results suggested that the submicron lipid emulsion is a promising intravenous carrier for docetaxel in place of its present commercially available docetaxel micellar solution with potential toxic effects.     

Eudragit S100 coated microsponges for Colon targeting of prednisolone

Context: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease.

Objective: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery.

Materials and methods: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72?kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release.

Results: PLMs were found to be nano-porous spherical microstructures with size around 35?µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1?hr in SGF (pH 1.2), 2 to 3?h in SIF (pH 4.6), 4–5?h in SIF (pH 6.8), and 6–24?h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24?h.

Discussion and conclusion: In vitro drug release studies revealed that drug starts releasing after 5?h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.     

Development of Extended Release Dosage Forms Using Non-Uniform Drug Distribution Techniques

ABSTRACT

Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37°C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.     

Preparation And Evaluation of A Long Acting Liquied Antitussive Product

Abstract

Microparticles containing a dextramothophan-resins complex were prepared by a modified emulsion solvent evaporation method. The particles were evaluated for size distribution and dissolution rate. Selected microparticles were suspended in various liquid media and stored at room tempertature. Dissolution of suspended in various liquid media and stored at room temperature. Dissolution of suspended microparticles was studied after storage up to 40 days. The particles were found to be stable and did not release drug in a supending media containing 30% propylene glycol, 35% syrup and 35% of 1% methylcellulose 1500 cps solution.     

Determination of the Acidic Degradation Products,Acetic, Propionic,Butyric, and Phthalic Acid in Aqueous Pseudolatexes of Cellulosic Esters by High Performance Liquid Chromatography

Abstract

An isocratic, reversed-phase HPLC method was developed to quantify the organic acids, acetic, propionic, butyric, and phthalic acid, formed as a result of ester hydrolysis, in pseudolatexes of cellulosic esters. Colloidal dispersions of cellulose acetate, cellulose acetate butyrate, and cellulose acetate propionate were prepared by a microfluidization-solvent evaporation method. Dispersions of cellulose acetate phthalate were prepared by redispersion of a spraydried commercial pseudolatex. The acids were detected at 210 nm, the mobile phase being 0.025 M phosphate buffer: methanol (80:20 v/v%, pH 3.0). The peak height response was linear over the studied concentration range of 2 – 10 mM/L for the aliphatic acids and 20–100 μM/L for phthalic acid. The minimum detectable quantities for acetic, propionic, butyric, and phthalic acid were 0.02 mM/L, 0.05 mM/L, 0.1 mM/L, and 0.0005 mM/L, corresponding to a % change in acetyl, propionyl, butyryl, and phthalyl content of 4.0 × 10⁴, 1.2 × 10³, 2.9 × 10³, and 2.8 × 10^?5 for a 30% w/v pseudolatex. The colloidal polymer particles were separated by ultracentrifugation, filtration, or flocculation with aluminum chloride solution before analysis of the aqueous phase. Similar acid concentrations were obtained for the three separation methods. The recovery from spiked samples was almost complete for acetic, approximately 90% for propionic acid, and less than 80% for butyric acid.