The Release of an Ampholytic Drug from Acrylic Films

Benzyloxiamine was used as an ampholytic drug model to study the in vitro drug release from films in a function of pH. Two films based on commercial acrylic dispersions Scopacryl^R and Eudragit^R were used as drug carriers. The films investigated were produced by a solvent east technique. The pH into the films was adjusted at every experiment before cast

To understand the factors governing the release of the ampholytic drug its protonation/ionization macro and microconstants have been determined. The protonation macroconatants determined were log K₁= 7.80, log K₂ = 4.26 and log B₂= 12.06. The microconstants calculated were log K^f= 7.79, log K^a= 4.74, log K_a^f = 7.33 and log K_f^a = 4.29.

The release data could be interpreted by taking into account species concentrations calculated by use these constants on the one hand and the velocity and diffusion coefficients on the other.     

Relationship Between film Properties and Drug Release from Acrylic Films

Abstract

An in vitro technique was used to determine the release rates of drugs from different acrylic copolymers as carrier systems. The drugs used in this investigation were pilocarpine, streptomycine, isosorbide salts and nitroglycerol. By applying the Higuchi equations the diffusion coefficients of the drugs were calculated. A tensile stress test was used to examine certain mechanical properties of the films.

It was found that the incorporation of drugs into acrylic films by different techniques allowed the facile preparation of various compositions with diffusion coefficients in a relativly large range (10^-8…10^-15cm² s^-1). The choice of the physicochemical state of the drug and the film composition can significantly affect drug release. The strain of the films depended on the tensile stress, the water and additives content.

It was examined that the drug release depended on the mechanical properties of the films. In general the drug release was faster from the lower viscosity grades and higher humidity contents of the films. This can be done by modifying the chemical structure of the used polymer system or by making use additives with alcoholic groups.     

Controlled Release of a Poorly Water-Soluble Drug from Hot-Melt Extrudates Containing Acrylic Polymers

ABSTRACT

Controlled release tablets containing a poorly water-soluble drug, indomethacin (IDM), acrylic polymers (Eudragit® RD 100, Eudragit® L 100, or Eudragit® S 100), and triethyl citrate (TEC) were prepared by hot-melt extrusion. The physicochemical and IDM release properties of the controlled release hot-melt extrudates were investigated. Indomethacin (IDM) was found to be both thermally and chemically stable following hot-melt extrusion processing and displayed a plasticizing effect on Eudragit® RL PO as demonstrated by a decrease in the glass transition temperatures of the polymer. The inclusion of either Pluronic® F68, Eudragit® L 100, or Eudragit® S 100 in the powder blend containing Eudragit® RD 100 prior to processing increased the rate of release of the IDM from the extrudates. An increase in the media pH and a decrease in the granule particle size also increased the rate of release of IDM. The inclusion of TEC up to 8% in the granule formulation or compressing the granules into tablets had no significant effect on the drug release rate. Indomethacin (IDM) was transformed from a crystalline Form I into an amorphous form in the Eudragit® RD 100 granules following hot-melt extrusion. The thermal processing facilitated the formation of a solid solution with a continuous matrix structure that was shown to control drug diffusion from the extrudates.     

The Kinetics of Drug Release from Ethylcellulose Solid Dispersions

Abstract

Sulphadiazine - ethylcellulose (EC) solid dispersions with different drug: carrier ratios were prepared and fractionated. In vitro drug release followed an apparent zero-order kinetics rate constant being dependent on the thickness of the coat which was the rate controlling step in the process. Drug release was found to increase as the granule size was decreased. The amount of drug released was found to be pH dependent thus showing the existence of pores in the coat surrounding the drug particles. Inclusion of polyethylene glycol or sodium lauryl sulphate in the coat material or dissolution medium resulted in increased dissolution, an effect which was attributed to increase in porosity, reduction of interfacial tension and increase in wettability which was associated with the presence of these compounds.     

The Control of Drug Release from Conventional Melt Granulation Matrices

Sustained release potassium chloride tablets were prepared using a melt granulation formulation in a Baker Perkins Granulator. Parts of the validation for this manufacturing process are highlighted in this paper including granulation end point temperature, incorporation of extragranular excipients, amount of wax in the formulation, granule cooling rate and scale of the operation. A number of other factors have been studied which are not Included here although they are no less important. The release of potassium chloride from tablets was found to be dependent on the wax level and the amount of extragranular excipients (“wicklng agent”). Within the controlled production process, any variation in granulation end point temperature and granule cooling rate should not have any significant effect.     

The Control of Drug Release from Conventional Melt Granulation Matrices

Abstract

Sustained release potassium chloride tablets were prepared using a melt granulation formulation in a Baker Perkins Granulator. Parts of the validation for this manufacturing process are highlighted in this paper including granulation end point temperature, incorporation of extragranular excipients, amount of wax in the formulation, granule cooling rate and scale of the operation. A number of other factors have been studied which are not Included here although they are no less important. The release of potassium chloride from tablets was found to be dependent on the wax level and the amount of extragranular excipients (“wicklng agent”). Within the controlled production process, any variation in granulation end point temperature and granule cooling rate should not have any significant effect.     

Dissolution Controlled Drug Release from Agarose Beads

Abstract

A simple method was used for loading ibuprofen or indomethacin into agarose beads to obtain sustained release. Placebo beads were prepared by a dropwise addition of a hot aqueous agarose solution into a beaker of chilled mineral oil and water. Prior to loading, the aqueous component in the beads was replaced by repeated soakings in ethanol. Loading was accomplished at room temperature using ethanolic drug solutions. Upon drying, the beads shrank to about a third of their original size. The surface morphology of dried placebo and loaded beads was studied using electron microscopy. The release time at 37° C and pH 7.5 increased with drug loading and at 50% loading the release time was 4 hours for indomethacin and 6 hours for ibuprofen. Release of chlorpheniramine from dried and swollen beads was examined to elucidate the release mechanism. From dissolution studies it was concluded that the delay due to swelling is less than 10 minutes, chlorpheniramine release from swollen beads was primarily diffusion controlled, and the release mechanism for indomethacin and ibuprofen has three components: i) swelling of the beads, ii) dissolution of crystallized drug, and iii) diffusion of dissolved drug from the beads.     

Testing of Drug Release from Bioadhesive Vaginal Tablets

To establish en in vitro test method that can predict the drug release and dissolution behaviour of vaginal bioadhesive controlled release tablets, a system was developed and its appropriateness to the in situ conditions was examined. For this purpose, the dissolution rates of vaginal bioadhesive tablets were measured by three different methods. These were, USP dissolution apparatus two and a new vaginal dissolution tester (NVDT) which was developed by us with some modification of the vaginal tablet desentegration apparatus of BP 1988 and, testing in cow vaginas in situ. Four different bioadhesive tablet formulations were used being composed of the drug and the anionic polymer, polyacrylic acid (PAA) and the nonionic polymers, hydroxypropylmethyl cellulose (HPMC) and ethyIcellulose (EC). The release profiles of the in vitro and in situ methods were investigated and evaluated kinetically.

It was found that NVDT could be used to investigate the drug release from vaginal tablets.     

Role of Surfactant on Drug Release from Tablets

Abstract

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Role of Surfactant on Drug Release from Tablets

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Testing of Drug Release from Bioadhesive Vaginal Tablets

Abstract

To establish en in vitro test method that can predict the drug release and dissolution behaviour of vaginal bioadhesive controlled release tablets, a system was developed and its appropriateness to the in situ conditions was examined. For this purpose, the dissolution rates of vaginal bioadhesive tablets were measured by three different methods. These were, USP dissolution apparatus two and a new vaginal dissolution tester (NVDT) which was developed by us with some modification of the vaginal tablet desentegration apparatus of BP 1988 and, testing in cow vaginas in situ. Four different bioadhesive tablet formulations were used being composed of the drug and the anionic polymer, polyacrylic acid (PAA) and the nonionic polymers, hydroxypropylmethyl cellulose (HPMC) and ethyIcellulose (EC). The release profiles of the in vitro and in situ methods were investigated and evaluated kinetically.

It was found that NVDT could be used to investigate the drug release from vaginal tablets.     

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.     

Spheronization II: Drug Release from Drug-Diluent Mixtures

Abstract

Pellets were prepared from wet granulations using an extruder and spheronizer. Binary mixtures of active ingredient and different types of Avicel micro-crystalline cellulose products have been processed and evaluated to determine the effect of varying the drug, the diluent, and the drug-diluent ratio. Physical properties including in-vitro drug release profiles were evaluated for the uncoated pellets. Anhydrous Theophylline, USP and Quinidine Sulfate, USP were evaluated at drug-diluent ratios from 10:90 to 80:20. Chlorpheniramine Maleate, USP and Hydrochlorothiazide, USP were incorporated into one system to study the influence of more extreme values of aqueous solubility on drug release. Drug release was found to vary with the drug, diluent, and the drug-diluent ratio.     

Some Factors Affecting the Release of Drug from Membrane Coated Slow Release Tablets

Tablets containing sodium salicylate were prepared by direct compression and coated with ethylcellulose and polyethylene glycol 3350. The effect of drug loading, direct compression carrier type, polymer ratio in the coating solution, pH of the dissolution medium, and agitation speed on the drug release were investigated using the USP XXI paddle method. It was observed that direct compression carriers, ratio of ethyl cellulose to polyethylene glycol, the amount of drug present in the tablet, and agitation speed used did not have any influence on the drug release from coated tablets, while the pH of the dissolution medium (gastric vs. intestinal fluids) was found to affect the drug release.     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Spheronization II: Drug Release from Drug-Diluent Mixtures

Pellets were prepared from wet granulations using an extruder and spheronizer. Binary mixtures of active ingredient and different types of Avicel micro-crystalline cellulose products have been processed and evaluated to determine the effect of varying the drug, the diluent, and the drug-diluent ratio. Physical properties including in-vitro drug release profiles were evaluated for the uncoated pellets. Anhydrous Theophylline, USP and Quinidine Sulfate, USP were evaluated at drug-diluent ratios from 10:90 to 80:20. Chlorpheniramine Maleate, USP and Hydrochlorothiazide, USP were incorporated into one system to study the influence of more extreme values of aqueous solubility on drug release. Drug release was found to vary with the drug, diluent, and the drug-diluent ratio.     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect and environmental pH. The cumulative amount of drug released was found to be in accordance with zero-order kinetics. The system can be modified within broad limits and have flexibility as well as a wide spectrum of applicability with respect to different types of drugs.