A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl₂ crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl₂, diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease.     

Whey protein and alginate hydrogel microparticles for insulin intestinal absorption: Evaluation of permeability enhancement properties on Caco-2 cells

The evaluation of encapsulated insulin intestinal absorption enhancement was investigated by in vitro methods. Insulin-loaded microparticles (INS-MP) made of whey protein (WP) and alginate (ALG) were prepared by a cold gelation technique. Effect of INS encapsulation toward trypsin and chymotrypsin degradation was performed. Permeability studies using in vitro (Caco-2 cells) experiments were conducted. INS was partially protected by encapsulation toward enzymatic degradation. Moreover INS transport experiments showed that WP and, in lesser extent, ALG were able to enhance INS absorption both as MP and as polymeric solutions by opening the tight junctions. These experiments reinforced the interest of encapsulation in WP/ALG hydrogel combination.     

Liquid phase coating to produce controlled-release alginate microspheres

This study explored a liquid phase coating technique to produce polymethyl methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a mean diameter of 85.6?µm were prepared using an emulsification method. The alginate microspheres, as cores, were then coated with different types of PMMA by a liquid phase coating technique. The release characteristics of these coated microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the influence of drug load on encapsulation efficiency were studied. The release of paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in SGF and SIF were similar as the rate-controlling polymer coat was insoluble in both media. Drug release from Eudragit S100-coated microspheres was more sustained in SGF than in SIF, due to the greater solubility of the coating polymer in media with pH greater than 7.0. The drug release rate was affected by the core:coat ratio. Drug release from the coated microspheres was best described by the Higuchi's square root model. The liquid phase coating technique developed offers an efficient method of coating small microspheres with markedly reduced drug loss and possible controlled drug release.     

Liquid phase coating to produce controlled-release alginate microspheres

This study explored a liquid phase coating technique to produce polymethyl methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a mean diameter of 85.6 microm were prepared using an emulsification method. The alginate microspheres, as cores, were then coated with different types of PMMA by a liquid phase coating technique. The release characteristics of these coated microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the influence of drug load on encapsulation efficiency were studied. The release of paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in SGF and SIF were similar as the rate-controlling polymer coat was insoluble in both media. Drug release from Eudragit S100-coated microspheres was more sustained in SGF than in SIF, due to the greater solubility of the coating polymer in media with pH greater than 7.0. The drug release rate was affected by the core:coat ratio. Drug release from the coated microspheres was best described by the Higuchi's square root model. The liquid phase coating technique developed offers an efficient method of coating small microspheres with markedly reduced drug loss and possible controlled drug release.     

Mucoadhesive and floating chitosan-coated alginate beads for the controlled gastric release of amoxicillin

This work focused on the development of mucoadhesive and floating chitosan-coated alginate beads as a gastroretensive delivery vehicle for amoxicillin, towards the effective eradication of Helicobacter pylori, a major causative agent of peptic ulcers. Alginate was used as the core bead core polymer and chitosan as the mucoadhesive polymer coating. Amoxicillin-loaded alginate beads coated with 0.5% (w/v) chitosan (ALG/0.5%CHI) exhibited excellent floating ability, high encapsulation efficiency, high drug loading capacity, and a strong in vitro mucoadhesion to the gastric mucosal layer. In vitro, amoxicillin was released faster in simulated gastric fluid (pH 1.2, HCl) than in simulated intestinal fluid (phosphate buffer, pH 7.4). ALG/0.5%CHI could be prepared with a > 90% drug encapsulation efficiency and exhibited more than 90% muco-adhesiveness, 100% floating ability, and achieved sustained release of amoxicillin for over six hours in SGF.     

Increased Intestinal Delivery of Viable Saccharomyces boulardii by Encapsulation in Microspheres

Purpose Although probiotics are of a major potential therapeutic interest, their efficacy is usually limited by poor bioavailability of viable microorganisms on site. The aim of this study was to protect the probiotic Saccharomyces boulardii from degradation in order to ensure a greater number of viable yeast in the colon. Methods Alginate microspheres coated with or not with chitosan were used to encapsulate the yeast by an extrusion method. The efficiency of encapsulation was assessed both in vitro and in vivo. Results In vitro, less than 1% of the non-encapsulated probiotic survived after 120 min at pH 1.1, whereas the majority of encapsulated yeast cells remained entrapped within both types of microspheres. Further exposure to a pH 6.8 allowed the release of about 35% of viable yeasts. In vivo, the percentage of viable yeast excreted over 96 h after a single oral dose of 2 × 10⁸ cfu/100 g in rats was 2.5% for non-encapsulated yeast and reached 13.3 and 9.0% of the dose administered for the uncoated and chitosan-coated microspheres, respectively. Conclusions Given the dose-dependent efficacy of S. boulardii and the efficiency of microencapsulation in protecting the yeast from degradation, alginate microspheres could be of great interest in therapeutic applications of the yeast.     

Efficacy of Mucoadhesive Hydrogel Microparticles of Whey Protein and Alginate for Oral Insulin Delivery

Purpose

To evaluate the efficacy of mucoadhesive insulin-loaded whey protein (WP) /alginate (ALG) microparticles (MP) for oral insulin administration.

Methods

Insulin-loaded microparticles (ins-MP) made of whey protein and alginate were prepared by a cold gelation technique and an adsorption method, without adjunction of organic solvent in order to develop a biocompatible vehicle for oral administration of insulin. In vitro characterization, evaluations of ins-MP in excised intestinal tissues and hypoglycaemic effects after intestinal administration in healthy rats were performed

Results

The release properties and swelling behaviors, investigated in different pH buffers, demonstrated a release based on diffusion mechanism following matrix swelling. Mucoadhesion studies in rabbits and insulin transport experiments with excised intestinal rat tissues revealed that encapsulation in microparticles with mucoadhesive properties promotes insulin absorption across duodenal membranes and bioactivity protection. In vivo experiments reinforced the interest of encapsulation in whey protein/alginate combination. Confocal microscopic observations associated with blood glucose levels bring to light duodenal absorption of insulin biologically active following in vivo administration.

Conclusions

Insulin-loaded WP/ALG MP with high quantities of drug entrapped, in vitro matrix swelling and protective effect as well as excellent mucohadesive properties was developped. Improvement of intestinal delivery of insulin and increased in bioavailability were recorded.     

Entrapment efficiency and release characteristics of polyethyleneimine-treated or -untreated calcium alginate beads loaded with propranolol-resin complex

Propranolol-HCl-loaded calcium alginate (ALG) beads, propranolol-resin complex (resinate)-loaded calcium alginate (RALG) beads and polyethyleneimine (PEI)-treated RALG (RALG-PEI) beads were prepared by ionotropic gelation/polyelectrolyte complexation method. The beads were evaluated and compared in respect of drug entrapment efficiency (DEE) and release characteristics in simulated gastric fluid (SGF, 0.1(N) HCl, pH 1.2) and simulated intestinal fluid (SIF, phosphate buffer, pH 6.8). DEE of RALG beads was considerably higher than that of ALG beads containing unresinated drug. However, DEE of RALG beads decreased with increase in both gelation time and concentration of the gel forming Ca2+ ions due to drug displacement from resinate. PEI treatment of RALG beads further decreased DEE as the polycation also displaced the drug from the resinate. The release of drug from all the beads was slow and incomplete in SGF owing to considerably less swelling of the beads and the decrease in drug release from the beads followed the order: RALG-PEI相似文献   

A novel impinging aerosols method for production of propranolol hydrochloride-loaded alginate gel microspheres for oral delivery

Propranolol hydrochloride was directly encapsulated in alginate gel microspheres (40-50?μm in diameter) using a novel method involving impinging aerosols of CaCl(2) cross-linking solution and sodium alginate solution containing the drug. Microspheres formulated using 0.1?M CaCl(2) exhibited the highest drug loading (14%, w/w of dry microspheres) with 66.5% encapsulation efficiency. Less than 4% and 35% propranolol release occurred from hydrated and dried microspheres, respectively, in 2?h in simulated gastric fluid (SGF). The majority of the drug load (90%) was released in 5 and 7?h from hydrated and dried microspheres, respectively, in simulated intestinal fluid (SIF). Prior incubation of hydrated microspheres (cross-linked using 0.5?M CaCl(2)) in SGF prolonged the time of release in SIF to 10?h, which has implications for the design of protocols and correlation with in?vivo release behaviour. Restricted propranolol release in SGF and complete extraction in SIF demonstrate the potential of alginate gel microspheres for oral delivery of pharmaceuticals.     

Cross-linking of hard gelatin carbamazepine capsules: effect of dissolution conditions on in vitro drug release.

The aim of this study was to determine if the use of both enzyme and surfactant in the dissolution medium changes the in vitro drug release from cross-linked hard gelatin capsules containing a water-insoluble drug. Hard gelatin capsules were cross-linked by a controlled exposure to formaldehyde resulting in different stressed capsules and carbamazepine (CBZ) was chosen as a drug model. In vitro dissolution studies were conducted using simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) with enzymes. Sodium lauryl sulfate (SLS) was added in the dissolution medium at a concentration of 2% m/v both in SGF and SIF with pepsin and pancreatin, respectively. The percentage of CBZ dissolved was reduced by increasing the degree of gelatin cross-linking. For unstressed hard gelatin capsules, 36% of the CBZ was released after 1 h, lowering to 5% for highly stressed hard gelatin capsules in the SGF. A similar effect was observed with SIF. In the case of moderately stressed hard gelatin capsules, addition of enzyme in the dissolution medium enhanced the percentage of CBZ dissolved. The dissolution level increased from 12% to 39% in SGF with pepsin for hard gelatin capsules cross-linked with 1500 ppm formaldehyde. On the contrary, the use of enzyme in the dissolution medium did not increase the dissolution of CBZ from highly stressed hard gelatin capsules. Surprisingly, the addition of SLS in the medium did not allow the release of the CBZ both in SGF and in SIF. The results of this study demonstrate that the use of enzyme in the dissolution medium is justified for moderately cross-linked hard gelatin capsules. However, the action of a surfactant added in the medium containing enzyme remains unclear.     

Fabrication of drug-loaded biodegradable microcapsules for controlled release by combination of solvent evaporation and layer-by-layer self-assembly

The initial burst release of drug from polymer microparticles remains an unsolved problem. Here, we deposited polysaccharides on drug-loaded microspheres using layer-by-layer self-assembly to produce core-shell microparticles for sustained drug release. The ibuprofen (IBU)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were fabricated by conventional solvent evaporation. The processing parameters, such as pH of water phase, drug/polymer ratio, polymer type, and emulsifier concentration, were optimized according to the encapsulation efficiency and drug loading as pH 4.0, drug/polymer ratio=10/50 (wt), HV in PHBV=6wt.%, and PVA concentration=1% (w/v). The multilayer shells of chitosan (CHI)/sodium alginate (ALG) and poly(diallyldimethylammonium chloride) (PD)/sodium poly(styrenesulfonate) (PSS) were formed on the IBU-loaded PHBV microparticles using layer-by-layer self-assembly. The in vitro release experiments revealed that, as for the microparticles with three CHI/ALG bilayer shells, the initial burst release of IBU from the microparticles was significantly suppressed and the half release time was prolonged to 62h from 1h for the microparticles without coverage. The compact CHI/ALG multilayer film was observed with an atomic force microscopy (AFM) due to the matched distance of charges along the CHI chain and those along the ALG chains. The present combination for encapsulating drug-loaded microparticles demonstrates an effective way to prolong the drug release with reduced initial burst.     

Novel alginate gel microspheres produced by impinging aerosols for oral delivery of proteins

Lysozyme and insulin were encapsulated in alginate gel microspheres using impinging aerosols method. High loadings of around 50% weight/dry microspheres weight were obtained with encapsulation efficiencies of at least 48%. Environmental scanning electron microscopy revealed smooth spherical hydrated microspheres (30–60?µm) in diameter. No lysozyme or insulin release was measured in simulated gastric fluid (HCl, pH 1.2, 37°C). Total insulin release occurred in simulated intestinal fluid (SIF; phosphate buffer saline, pH 7.4, 37°C) in 8?h following 2?h incubation in SGF and was found to retain 75% activity using the ARCHITECT® assay. Lysozyme was released completely in SIF in 10?h following 2?h incubation in SGF and was found to exhibit at least 80% bioactivity using the Micrococcus lysodeikticus assay. The absence of protein release in HCl and the retention of high levels of biological activity demonstrate the potential of alginate gel microspheres, for improving oral delivery of biopharmaceuticals.     

Formulation strategies for achieving high delivery efficiency of thymoquinone-containing Nigella sativa extract to the colon based on oral alginate microcapsules for treatment of inflammatory bowel disease

Nigella sativa extract (NSE) was incorporated in alginate microcapsules using aerosolisation and homogenisation methods, respectively, with the aim of delivering high concentrations of the active species, thymoquinone (TQ), directly to sites of inflammation in the colon following oral administration. Encapsulation of NSE was accomplished either by direct loading or diffusion into blank microparticles. Microcapsules in the size range 40–60 µm exhibited significantly higher NSE loading up to 42% w/w and encapsulation efficiency (EE) up to 63% when the extract was entrapped by direct encapsulation compared with 4.1 w/w loading, 6.2% EE when NSE was incorporated by diffusion loading. Sequential exposure of samples to simulated intestinal fluids (SIFs) revealed that the microcapsules suppressed NSE release in simulated gastric fluid (SGF) for 2?h and SIF for 4?h and liberated most of the NSE content (80%) in simulated colonic fluid (SCF) over 18?h. NSE released in SCF at 12?h exhibited antioxidant activity, when measured using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay at levels comparable with the activity of unencapsulated extract. These findings demonstrate the potential of oral alginate microcapsules as highly efficient, targeted carriers for colonic delivery of NSE in the treatment of inflammatory bowel disease.     

Collagen-coated polycaprolactone microparticles as a controlled drug delivery system

Objective: Polycaprolactone (PCL) microparticles coated with acetylated collagen have been assessed for use as a controlled drug delivery system.

Method: The surface morphology, drug encapsulation and release profile of PCL microparticles and collagen-coated PCL microparticles containing doxycycline hydrochloride (DH) have been investigated in order to develop a controlled release system which would in addition act as a scaffold for cell attachment. PCL microparticles were prepared by emulsion solvent evaporation technique and loaded with DH. Since the encapsulation was found to be low, PCL microparticles were coated with acetylated collagen containing DH, to increase the drug availability. Collagen was modified by acetylation to shift its isoelectric point and to have acetylated collagen solution at pH 7.0. The microparticles were characterized using a scanning electron microscope (SEM) and the in vitro drug release profile was determined using HPLC.

Results: Uniform sized (～1000 nm) PCL microparticles were prepared using 4% PVA in the external water phase. Acetylated collagen at pH 7.0 was coated onto the PCL microparticles. This resulted in microparticles of uniform size at neutral pH. PCL acts as a support for collagen which acts as a scaffold for cell attachment. In vitro drug release studies show that collagen-coated PCL microparticle is a promising candidate for controlled drug delivery system having release duration of over 10 days. In vitro fibroblast culture studies reveal that collagen is a good substrate for cell attachment and would provide a stable environment for cell proliferation and regeneration. Thus, this system would be ideal for a short-term drug delivery to create an aseptic environment where cells can adhere and proliferate to regenerate the site.     

Novel alginate gel microspheres produced by impinging aerosols for oral delivery of proteins

Lysozyme and insulin were encapsulated in alginate gel microspheres using impinging aerosols method. High loadings of around 50% weight/dry microspheres weight were obtained with encapsulation efficiencies of at least 48%. Environmental scanning electron microscopy revealed smooth spherical hydrated microspheres (30-60 μm) in diameter. No lysozyme or insulin release was measured in simulated gastric fluid (HCl, pH 1.2, 37°C). Total insulin release occurred in simulated intestinal fluid (SIF; phosphate buffer saline, pH 7.4, 37°C) in 8 h following 2 h incubation in SGF and was found to retain 75% activity using the ARCHITECT? assay. Lysozyme was released completely in SIF in 10 h following 2 h incubation in SGF and was found to exhibit at least 80% bioactivity using the Micrococcus lysodeikticus assay. The absence of protein release in HCl and the retention of high levels of biological activity demonstrate the potential of alginate gel microspheres, for improving oral delivery of biopharmaceuticals.     

酸敏性葡聚糖纳米凝胶的制备与释药性质考察

目的制备具有酸敏特性的聚（甲基丙烯酸缩水甘油酯修饰葡聚糖,dex GMA）/（丙烯酸,AAc）纳米凝胶,研究其降解和释药性质。方法乳液聚合法制备poly(dex GMA/AAc)纳米凝胶,测定不同pH值下的粒度分布,以红霉素（EM）为药物模型,动态透析法测定纳米凝胶在不同pH值下的释药性质。结果poly(dex GMA/AAc)纳米凝胶的平均粒径约为100 nm,包裹率、载药率分别为90.7%和1.06%。在无酶人工胃液 (SGF) 2 h纳米凝胶的药物累积释放率分别为7.0%,之后在无酶人工肠液(SIF)里4 h 内增加到37.0%。结论poly(dex GMA/AAc)纳米凝胶具有酸敏特性,在SGF里释放少量药物,在SIF里凝胶溶胀、降解,药物释放量明显增大。poly(dex GMA/AAc)纳米凝胶是潜在的结肠靶向载体。     

Microencapsulation of Chlorpheniramine Maleate–Resin Particles with Crosslinked Chitosan for Sustained Release

ABSTRACT

Formulation and preparation parameters of drug/ion-exchange particles microencapsulated in cross-linked chitosan were evaluated for controlled release of the water-soluble drug chlorpheniramine maleate (CPM) in a suspension. An emulsion solvent evaporation method was used to produce CPM-resinates embedded in glutaraldehyde (GTA) crosslinked chitosan microspheres (MCSs). Crosslinking extent in the chitosan was monitored by swelling measurements. Controlled release was evaluated by dissolution tests in simulated gastric fluid without enzyme (SGF) and in simulated intestinal fluid without enzyme (SIF). CPM-resinates contained 62% (w/w) of drug. MCSs were spherical, ranging from 82 to 420 μm in diameter, and contained multiple resinates. The sizes of MCSs prepared with safflower oil and Span 80 were controlled by surfactant concentration, stirring speed, and duration of stirring. Maximum crosslinking was produced with 240 mg GTA per 250 mg of chitosan. Maximum drug release from free CPM-resinates was about 60% by 1 hr in SGF, and was about 100% by 3 hr in SIF. CPM release was slower from MCSs crosslinked with 120 mg of GTA compared to 5 mg GTA in both media. By 8.3 hr, the more crosslinked MCSs released about 30% CPM in SGF, and about 60% in SIF. Because of the apparent ceiling on release in SGF, the final experiments were conducted in SIF. Increasing the weight ratio of the chitosan coating to CPM-resinate ratio from 1:1 to 4:1 moderately decreased release profiles carried out to 33 hr. Increasing MCS diameters from 82 to 163 μm moderately decreased release profiles. Microencapsulation of CPM-resinates with crosslinked chitosan demonstrated controlled release of CPM in SGF and SIF without enzymes. The retardation effect increased when the crosslinking extent and chitosan to resin ratio increased.     

Formulation,in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles

Abstract

Context: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs).

Objective: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs.

Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter’s Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver.

Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49?±?0.04 to 4.03?±?0.05.

Discussion: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H₂ and H₃) compared with SGF (13 and 18% for H₂ and H₃ respectively) after 8?h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver.

Conclusion: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.     

Microencapsulation of a probiotic bacteria with alginate–gelatin and its properties

Lactobacillus casei ATCC 393-loaded microcapsules based on alginate and gelatin had been prepared by extrusion method and the product could increase the cell numbers of L. casei ATCC 393 to be 10⁷ CFU g^?1 in the dry state of microcapsules. The microparticles homogeneously distributed with size of 1.1 ± 0.2 mm. Four kinds of microcapsules (S₁, S₂, S₃ and S₄) exhibited swelling in simulated gastric fluid (SGF) while the beads eroded and disintegrated rapidly in simulated intestinal fluid (SIF). Cells of L. casei ATCC 393 could be continuously released from the microcapsules during simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than that in SGF. Encapsulation in alginate–gelatin microcapsules successfully improved the survival of L. casei ATCC 393 and this approach might be useful in delivery of probiotic cultures as a functional food.     

Microencapsulation of chlorpheniramine maleate-resin particles with crosslinked chitosan for sustained release

Formulation and preparation parameters of drug/ion-exchange particles microencapsulated in cross-linked chitosan were evaluated for controlled release of the water-soluble drug chlorpheniramine maleate (CPM) in a suspension. An emulsion solvent evaporation method was used to produce CPM-resinates embedded in glutaraldehyde (GTA) crosslinked chitosan microspheres (MCSs). Crosslinking extent in the chitosan was monitored by swelling measurements. Controlled release was evaluated by dissolution tests in simulated gastric fluid without enzyme (SGF) and in simulated intestinal fluid without enzyme (SIF). CPM-resinates contained 62% (w/w) of drug. MCSs were spherical, ranging from 82 to 420 microns in diameter, and contained multiple resinates. The sizes of MCSs prepared with safflower oil and Span 80 were controlled by surfactant concentration, stirring speed, and duration of stirring. Maximum crosslinking was produced with 240 mg GTA per 250 mg of chitosan. Maximum drug release from free CPM-resinates was about 60% by 1 hr in SGF, and was about 100% by 3 hr in SIF. CPM release was slower from MCSs crosslinked with 120 mg of GTA compared to 5 mg GTA in both media. By 8.3 hr, the more crosslinked MCSs released about 30% CPM in SGF, and about 60% in SIF. Because of the apparent ceiling on release in SGF, the final experiments were conducted in SIF. Increasing the weight ratio of the chitosan coating to CPM-resinate ratio from 1:1 to 4:1 moderately decreased release profiles carried out to 33 hr. Increasing MCS diameters from 82 to 163 microns moderately decreased release profiles. Microencapsulation of CPM-resinates with crosslinked chitosan demonstrated controlled release of CPM in SGF and SIF without enzymes. The retardation effect increased when the crosslinking extent and chitosan to resin ratio increased.