Effects of Hydrophilic Excipients and Compression Pressure on Physical Properties and Release Behavior of Aspirin-Tableted Microcapsules

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

Effects of hydrophilic excipients and compression pressure on physical properties and release behavior of aspirin-tableted microcapsules.

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

Development of Hollow Microspheres as Floating Controlled-Release Systems for Cardiovascular Drugs: Preparation and Release Characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489–350 μm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.     

Development of hollow microspheres as floating controlled-release systems for cardiovascular drugs: preparation and release characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489-350 μm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Studies on the Release of Theophylline from Polyvinylacetate Microspheres

Polyvinylacetate microspheres containing theophylline were prepared by emulsification and solvent removal method. The release pattern of theophylline from the microspheres was found to be best explained by diffusion controlled process. The rates of release were found to be influenced by drug-polymer ratios, size of microspheres, concentration of surfactant used for the preparation of microspheres, and pH of the dissolution media.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Colloidal systems made of biotransesterified α, β and γ cyclodextrins grafted with C10 alkyl chains

Alpha (α), beta (β) and gamma (γ) fatty ester cyclodextrins with C10 alkyl chains (CD-C10) on the secondary face were synthesized using an enzymatic pathway involving thermolysin as a biocatalyser. Depending on the formulation, these new cyclodextrin derivatives self-assembled and formed nanostructures presenting the ability to entrap diazepam, a lipophilic model drug. The loaded nanoparticles were tested for in vitro release of the drug molecule. Biphasic release profiles were observed with a pronounced delayed release in the case of γCD-C10 nanoparticles, associated to a low initial burst effect. These results are encouraging and may constitute the basis for designing novel multifunctional nanoscale systems made up with versatile cyclodextrin derivatives.     

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.     

Formulation factors affecting drug release from poly(lactic acid) (PLA) microcapsule tablets

A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.     

Studies on the Release of Theophylline from Polyvinylacetate Microspheres

Abstract

Polyvinylacetate microspheres containing theophylline were prepared by emulsification and solvent removal method. The release pattern of theophylline from the microspheres was found to be best explained by diffusion controlled process. The rates of release were found to be influenced by drug-polymer ratios, size of microspheres, concentration of surfactant used for the preparation of microspheres, and pH of the dissolution media.     

Assessment of tailor-made HPMC-based matrix minitablets comprising a weakly basic drug compound

Tailor-made, pH-controlled matrix minitablets based on different HPMC types were developed comprising the weakly basic drug dipyridamole. The incorporation of pH modifiers, i.e., fumaric and succinic acid, enhanced the drug release at pH 6.8. Assessing the drug release, acid release, and the microenvironmental pH (pH_M) provided detailed understanding of pH-controlled mini-matrices.

The extent and duration of pH_M alteration was more pronounced in presence of fumaric acid. Minitablets based on the fast dissolving Methocel K100LV (≤ 100 cps) showed simultaneous release rates of dipyridamole and fumaric acid with a constant low average pH_M.     

Assessment of Tailor-Made HPMC-Based Matrix Minitablets Comprising a Weakly Basic Drug Compound

Tailor-made, pH-controlled matrix minitablets based on different HPMC types were developed comprising the weakly basic drug dipyridamole. The incorporation of pH modifiers, i.e., fumaric and succinic acid, enhanced the drug release at pH 6.8. Assessing the drug release, acid release, and the microenvironmental pH (pH_M) provided detailed understanding of pH-controlled mini-matrices.

The extent and duration of pH_M alteration was more pronounced in presence of fumaric acid. Minitablets based on the fast dissolving Methocel K100LV (≤ 100 cps) showed simultaneous release rates of dipyridamole and fumaric acid with a constant low average pH_M.     

Dissolution Characteristics of Polycaprolactone-Polylactide Microspheres of Chlorpromazine

Studies were conducted on the preparation of controlled release polycaprolactone-polylactide microcapsules of chlorpromazine and on release of the drug from the microcapsules in pH 7.0 buffer medium. A wide range of release rates of the drug was obtained by simple change in the polymer system. Chlorpromazine was released from the microspheres in a biphasic manner consisting of an initial fast release phase followed by a slow-release phase. Increasing the drug content increased the initial drug release rate but no significant drug loading effect on the second stage dissolution rate was noted. There was no significant effect of particle size on the drug release rate from the microspheres. The swelling property of the microspheres and the agglomerate nature of the sieve fractions may complicate the drug release kinetics and obscure the particle size effect on dissolution rate.     

Effect of formulation ingredients on the physical characteristics of salmeterol xinafoate microparticles tailored by spray freeze drying

Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HPβCD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10–30 μm. Dissolution of SX from processed particles was substantially higher (～90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (～22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin.     

Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R²?>?0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f₂?>?50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.     

Albumin Microspheres: effect of process Variables on size Distribution and in Vitro Release

Albumin microspheres used as target drug delivery systems were prepared from egg albumin by polymerization technique using glutaral dehyde as the cross linking agent. The present study was designed to evaluate the effect of process variables on the nicrosphere size distribution and in vitro drug release. Phase volume ratio and speed of agitation exerted greater influence on the microsphere size distribution whereas the albumin concentration and cross linking time effected only the yield and surface characteristics of the microspheres respectively. Lower phase volume ratios resulted in small and uniform microspheres with smooth surfaces in narrow size range. Speed of agitation exhibited an inverse relationship with size. In vitro release pattern of drug from the microspheres showed a biphasic profile and the release rates were prolonged upon increase in the concentration of cross linking agent and cross linking time.     

Dissolution Characteristics of Polycaprolactone-Polylactide Microspheres of Chlorpromazine

Abstract

Studies were conducted on the preparation of controlled release polycaprolactone-polylactide microcapsules of chlorpromazine and on release of the drug from the microcapsules in pH 7.0 buffer medium. A wide range of release rates of the drug was obtained by simple change in the polymer system. Chlorpromazine was released from the microspheres in a biphasic manner consisting of an initial fast release phase followed by a slow-release phase. Increasing the drug content increased the initial drug release rate but no significant drug loading effect on the second stage dissolution rate was noted. There was no significant effect of particle size on the drug release rate from the microspheres. The swelling property of the microspheres and the agglomerate nature of the sieve fractions may complicate the drug release kinetics and obscure the particle size effect on dissolution rate.     

Albumin Microspheres: effect of process Variables on size Distribution and in Vitro Release

Abstract

Albumin microspheres used as target drug delivery systems were prepared from egg albumin by polymerization technique using glutaral dehyde as the cross linking agent. The present study was designed to evaluate the effect of process variables on the nicrosphere size distribution and in vitro drug release. Phase volume ratio and speed of agitation exerted greater influence on the microsphere size distribution whereas the albumin concentration and cross linking time effected only the yield and surface characteristics of the microspheres respectively. Lower phase volume ratios resulted in small and uniform microspheres with smooth surfaces in narrow size range. Speed of agitation exhibited an inverse relationship with size. In vitro release pattern of drug from the microspheres showed a biphasic profile and the release rates were prolonged upon increase in the concentration of cross linking agent and cross linking time.     

Factorial Design of Phenylpropanolamine Prolonged Release Tablets Formulations Using Fluid Bed Dryer Granulator

A two level factorial design approach was applied to the formulation of prolonged release phenylpropanolamine tablets using three factors: Ethylacrylate-methyl meth-acrylate co-polymer (Eudragit NE-40D) concentration, Microcrystalline cellulose (Avicel PH102) addition to the tablets formula, and the milling of the granulations before compression. The release rate of the drug was the measured parameter. The rate of drug release was mainly affected by the level of the Eudragit. Avicel promotes the release of the drug, specially at low Eudragit level concentrations. Tablets prepared from unmilled lots showed slower drug release than the corresponding lots of milled granules.