Preparation and Evaluation of Mucin-Gelatin Mucoadhesive Microspheres for Rectal Delivery of Ceftriaxone Sodium

ABSTRACT

Soluble mucin (S-mucin) processed from the small intestines (ileal region) of freshly slaughtered pigs via homogenization, dialysis, centrifugation and lyophilization and its admixtures with type A gelatin were dispersed in an aqueous medium and used to formulate ceftriaxone sodium-loaded mucoadhesive microspheres by the emulsification cross-linking method using arachis oil as the continuous phase. The release profile of ceftriaxone sodium from the microspheres was evaluated in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). The microspheres were further evaluated as possible novel delivery system for rectal delivery of ceftriaxone sodium in rats. Release of ceftriaxone sodium from the microspheres in both release media was found to occur predominantly by diffusion following non-Fickian transport mechanism and was higher and more rapid in SIF than in SGF. The results obtained from this study may indicate that ceftriaxone sodium could be successfully delivered rectally when embedded in microspheres formulated with either type A gelatin alone or its admixtures with porcine mucin; hence providing a therapeutically viable alternative route for the delivery of this acid-labile third generation cephalosporin.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Oral Controlled Release Formulation for Highly Water‐Soluble Drugs: Drug–Sodium Alginate–Xanthan Gum–Zinc Acetate Matrix

An oral controlled release formulation matrix for highly water‐soluble drugs was designed and developed to achieve a 24‐hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH7.5) and simulated gastric fluid (SGF, pH1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24‐hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl–sodium alginate–xanthan gum–zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross‐linking structure. The cross‐linking structure might control a highly water‐soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels for oral controlled release drug delivery

This study evaluated the potential of stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug delivery carriers. Hydrogels were synthesized by graft copolymerization of the monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation technique. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting. XRD showed that the crystallinity of BC was reduced by grafting, whereas an increase in the thermal stability profile was observed in TGA. SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading. The hydrogels demonstrated a pH-responsive swelling behavior, with decreased swelling in acidic media, which increased with increase in pH of the media, reaching maximum swelling at pH 7. The release profile of the hydrogels was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that hydrogels may be suitable drug carriers for oral controlled release of drug delivery in the lower gastrointestinal tract.     

Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix

An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH7.5) and simulated gastric fluid (SGF, pH1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl-sodium alginate-xanthan gum-zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.     

Preparation of alginate-gelatin capsules and its properties

Capsules based on alginate and gelatin prepared by extrusion method could increase the cell numbers of Lactobacillus casei ATCC 393 to be 10⁸ CFU·g^-1 in the wet state of the capsules. The capsules were spherical, smooth-surfaced and non-aggregated with a diameter of (4.0 ± 0.3) mm. The behavior of the samples were quite similar at low relative humidity (33%, 52%) and the ratio of weight change reached 93%. Four kinds of capsules in simulated gastric fluid (SGF) exhibited shrinkage while the beads eroded accompanied with slight swelling in simulated intestinal fluid (SIF). The pH values affected the stability of the capsules and with the increase in pH, the capsules changed from shrank then swelled and finally, broke into pieces. The capsules behaved differently under different ion intensities and the introduction of gelatin weakened the stability of capsules compared with the alginate ones. Cells of L. casei ATCC 393 could be continuously released from the capsules in the simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than those in SGF.     

Preparation of alginate-gelatin capsules and its properties

Capsules based on alginate and gelatin prepared by extrusion method could increase the cell numbers of Lactobacillus casei ATCC 393 to be 10⁸ CFU·g⁻¹ in the wet state of the capsules. The capsules were spherical, smooth-surfaced and non-aggregated with a diameter of (4.0 ± 0.3) mm. The behavior of the samples were quite similar at low relative humidity (33%, 52%) and the ratio of weight change reached 93%. Four kinds of capsules in simulated gastric fluid (SGF) exhibited shrinkage while the beads eroded accompanied with slight swelling in simulated intestinal fluid (SIF). The pH values affected the stability of the capsules and with the increase in pH, the capsules changed from shrank then swelled and finally, broke into pieces. The capsules behaved differently under different ion intensities and the introduction of gelatin weakened the stability of capsules compared with the alginate ones. Cells of L. casei ATCC 393 could be continuously released from the capsules in the simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than those in SGF.     

Chitosan-Alginate Multilayer Beads for Gastric Passage and Controlled Intestinal Release of Protein

Abstract

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80–90% of the model protein within 12 h while multilayer beads released only 40–50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.     

Design and Evaluation of a Two-Layer Floating Tablet for Gastric Retention Using Cisapride as a Model Drug

A new kind of two-layer floating tablet for gastric retention (TFTGR) with cisapride as a model drug was developed. The in vitro drug release was determined, and the resultant buoyancy and the time-buoyancy curve were plotted. Because of the sodium bicarbonate added to the floating layer, when immersed in simulated gastric fluid (SGF) the tablet expands and rises to the surface, where the drug is gradually released. The in vitro drug release of this kind of two-layer dosage was controlled by the amount of hydroxypropylmethylcellulose (HPMC) in the drug-loading layer. Generally, the more HPMC, the slower the drug releases. Because cisapride has greater solubility in SGF than simulated intestinal fluid (SIF), its in vitro drug dissolution in SGF is faster than in SIF. One of the distinguishing characteristics of this kind of tablet is the separate regulation of buoyancy and drug release. The idea developed in this experiment can be used as a general model for the design of other tablets for gastric retention.     

Sustained release characteristics of tablets prepared with mixed matrix of sodium carrageenan and chitosan: effect of polymer weight ratio, dissolution medium, and drug type

The interpolymeric complexation of carrageenan and chitosan was investigated for its effect on drug release from polymeric matrices in comparison to single polymers. For this purpose, matrices with carrageenan: chitosan (CG:CS) ratios of 100%, 75%, 50%, 25%, and 0% were prepared at 1:1 drug to polymer ratio. The effect of dissolution medium and drug type on drug release from the formulations was addressed. Two model drugs were utilized: diltiazem HCl (DZ) as a salt of a basic drug and diclofenac Na (DS) as a salt of an acidic drug. Three dissolution media were used: water, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). Some combinations of the two polymers showed remarkable sustained release effect on DZ in comparison to the single polymers in water and SGF. However, no apparent effect for the combination on DZ release was shown in SIF. The medium effect was explained by the necessity of chitosan ionization, which could be attained by the acidic SGF or microacidic environment created by the used acidic salt of DZ in water, but not in SIF. An interaction between the medium type and CG:CS ratio was also found. With DS, the polymer combinations had similar dissolution profiles to those of the single polymers in water and SIF, which was explained by the lack of chitosan ionization by the medium or the drug basic salt. The dissolution profiles could not be obtained in SGF, which was attributed to the conversion of DS into diclofenac free acid. The importance of chitosan ionization for its interaction with CG to have an effect on the release of DS was demonstrated by performing dissolution of SGF presoaked tablets of DS in SIF, which showed an effect of combining the two polymers on sustaining the drug release.     

Zero-order release of theophylline from a core-in-cup tablet in sequenced simulated gastric and intestinal fluid

Core-in-cup tablets containing theophylline were evaluated for their dissolution characteristics in sequenced simulated gastric fluid (SGF) followed by simulated intestinalfluid (SIF). Core-in-cup tablets containing 10% w/w, 20% w/w, and 30% w/w acacia as binder were evaluated for their effects on the time course of release of theophylline. This was done to optimize a formula that could release theophylline at a zero-order rate of release for 8-16 hr in simulated gastrointestinal fluids. Theophylline was released and dissolved from the core-in-cup tablets at a rate that is more consistent with a zero-order dissolution rate than a first-order dissolution rate in both SIG and SIF. The dissolution rates of theophylline from the 10%, 20%, and 30% acacia core-in-cup tablets were 0.87 mg/min, 0.53 mg/min, and 0.27 mg/min, respectively in SGF, and 0.61 mg/min, 0.30 mg/min, and 0.20 mg/min, respectively in SIF. The results indicate that a concentration of 32% w/w acacia in the core tablet will release theophylline at a rate of 0.14 mg/min in SGF for 2 hr followed by SIF for 10 hr.     

Chitosan-alginate multilayer beads for gastric passage and controlled intestinal release of protein

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80-90% of the model protein within 12 h while multilayer beads released only 40-50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.     

Design and Evaluation of a Two-Layer Floating Tablet for Gastric Retention Using Cisapride as a Model Drug

A new kind of two-layer floating tablet for gastric retention (TFTGR) with cisapride as a model drug was developed. The in vitro drug release was determined, and the resultant buoyancy and the time-buoyancy curve were plotted. Because of the sodium bicarbonate added to the floating layer, when immersed in simulated gastric fluid (SGF) the tablet expands and rises to the surface, where the drug is gradually released. The in vitro drug release of this kind of two-layer dosage was controlled by the amount of hydroxypropylmethylcellulose (HPMC) in the drug-loading layer. Generally, the more HPMC, the slower the drug releases. Because cisapride has greater solubility in SGF than simulated intestinal fluid (SIF), its in vitro drug dissolution in SGF is faster than in SIF. One of the distinguishing characteristics of this kind of tablet is the separate regulation of buoyancy and drug release. The idea developed in this experiment can be used as a general model for the design of other tablets for gastric retention.     

pH-Controlled drug release from mesoporous silica tablets coated with hydroxypropyl methylcellulose phthalate

A simple pH-controlled drug release system was successfully prepared by coating pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) on drug-loaded mesoporous SBA-15 tablet. Using famotidine (Famo) as a model drug, the effects of coating times and drying temperature on drug release were studied in detail to optimize the drug release system. In simulated gastric fluid (SGF, pH 1.2), it took only 2 h for Famo to be completely released from mesoporous silica tablet without HPMCP coating. Also in SGF, with the increase of coating times and drying temperature, the release of Famo was greatly delayed by HPMCP coating. For the tablet with twice coating of HPMCP and dried at 80 °C, only 4.0 wt.% of Famo could be released within 4 h. However, in simulated intestinal fluid (SIF, pH 7.4), HPMCP coating did not show obvious effect on the release of Famo.     

pH-sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21?±?18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2?h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2?h, while nearly 90% of the drug was released within 6?h after transferring into SPDF.     

pH-Sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21?±?18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2?h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2?h, while nearly 90% of the drug was released within 6?h after transferring into SPDF.     

超声辅助合成多孔pH敏感性海藻酸钠水凝胶及其控释行为

利用超声波辅助接枝聚合制备多孔NaAlg-g-P(NVP-co-NHMAA)水凝胶,利用傅里叶红外光谱(FT-IR)、热重分析(TGA)和扫描电镜(SEM)对NaAlg-g-P(NVP-co-NHMAA)的结构和形态进行了表征,同时还研究了NaAlg-g-P(NVP-coNHMAA)的溶胀行为和pH敏感性。以5-氟尿嘧啶(5-FU)作为模型药物,研究了NaAlg-g-P(NVP-co-NHMAA)水凝胶在模拟胃液(SGF,pH=1.2)和模拟肠液(SIF,pH=7.4)下的控制释放行为,结果显示,在pH=7.4时,11h内该水凝胶的累积释放率高达80.2%,而在pH=1.2时只有50.2%,这表明NaAlg-g-P(NVP-co-NHMAA)水凝胶可以作为结肠靶向药物输送载体。     

Formulation design,in vitro characterizations and anti-malarial investigations of artemether and lumefantrine-entrapped solid lipid microparticles

Context: Poor aqueous solubility of artemether and lumefantrine makes it important to seek better ways of enhancing their oral delivery and bioavailability.

Objective: To formulate and carry out in vitro and anti-malarial pharmacodynamic evaluations of solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) of artemether and lumefantrine for oral delivery and improved bioavailability.

Materials and methods: Rational blends of Softisan^®154 and Phospholipon^®90H lipid matrices, and different concentrations of artemether and lumefantrine were used to formulate several batches of SLMs. Drug-free SLMs were also formulated. Morphology, particle size, encapsulation efficiency (EE%) and pH studies were performed. In vitro release studies were performed in alcoholic buffer, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. Anti-malarial pharmacodynamic studies were conducted in mice.

Results: Stable, smooth and spherical particles with sizes ranging from 4.2?±?0.02 to 9.3?±?0.8?µm were formed. EE% of 92.2–97.3% and 30.2–84.7% and pH of 3.0?±?0.02 to 4.9?±?0.12 and 3.0?±?0.02 to 5.8?±?0.05 were obtained for artemether and lumefantrine SLMs, respectively. Release of 100, 88.28 and 75.49%, as well as 63.26, 34.31 and 56.17% were recorded for artemether and lumefantrine in alcoholic buffer, SGF and SIF, respectively. Pharmacodynamic studies indicated very significant (p?Conclusion: Oral delivery and bioavailability of artemether and lumefantrine could be improved using SRMS-based SLMs.     

Basic drug--enterosoluble polymer coevaporates: development of oral controlled release systems

Precipitation of basic drugs within oral prolonged release systems, at the higher pH values of the intestine, would affect drug release. Coevaporates of a model basic drug verapamil HCl, in single or mixed polymer systems, containing Eudragit L100 (L100) and ethyl cellulose or Eudragit RS100, were prepared from ethanolic solution. XRD and DSC indicated loss of crystallinity of the drug in the coevaporates. The presence of the enterosoluble polymer in the system was found to aid in faster dissolution of the drug at higher pH values. This was affected by the presence and type of retarding polymer present in the system. Compression of the coevaporates resulted in either very slow release of the drug or undesirable changes in the release profile. Pelletization of a coevaporate containing drug and L100 yielded systems, which released the drug uniformly when studied by the buffer change method in simulated gastric (SGF) and intestinal (SIF) fluids. The presence of L100 in intimate contact with the drug was found to be essential for the desirable drug release properties of the system. The drug release occurred predominantly by diffusion in SGF and by a combination of diffusion and polymer dissolution/erosion in SIF. Appropriate choice of release modifiers and formulation variables and development of suitable formulations can yield systems which compensate for the reduced solubility of the drug in the higher pH environments of the intestine.