Evaluation of enteric matrix microspheres prepared by emulsion-solvent evaporation using scanning electron microscopy

Theophylline microspheres were prepared by the emulsion-solvent evaporation method using cellulose acetate butyrate (CAB381-20) and mixtures of CAB381-20(R) and cellulose acetate phthalate. The physical state of the drug, polymers and microspheres surfaces were determined using scanning electron microscopy. For those microspheres prepared using mixtures of CAB381-20 and cellulose acetate phthalate, scanning electron micrographs were taken before dissolution and also at different stages of dissolution (in SGF, pH 1.2 and in simulated intestinal fluid, pH 7.5). Micrographs were taken of the outside surfaces of the microspheres and of the cleaved microspheres showing their interiors (core). Drug crystals were observed on or near the surface of microspheres prepared from the polymer mixtures, while no drug particles or crystals were seen on the surfaces of microspheres prepared solely from CAB381-20. An acid wash for less than 2 min was capable of extracting all drug on the surface of the microspheres prepared from a mixture of CAB381-20 and cellulose acetate phthalate. The absence of drug crystals on the surface of CAB381-20 microspheres is believed to prevent initial drug release and create a lag time in release profiles. Results suggest that in both microsphere formulations, a layer of drug-free polymer is formed outside the core matrix and is believed to be responsible for the near zero-order release profiles.     

Evaluation of enteric matrix microspheres prepared by emulsion–solvent evaporation using scanning electron microscopy

Theophylline microspheres were prepared by the emulsion–solvent evaporation method using cellulose acetate butyrate (CAB381-20) and mixtures of CAB381-20® and cellulose acetate phthalate. The physical state of the drug, polymers and microspheres surfaces were determined using scanning electron microscopy. For those microspheres prepared using mixtures of CAB381-20 and cellulose acetate phthalate, scanning electron micrographs were taken before dissolution and also at different stages of dissolution (in SGF, pH 1.2 and in simulated intestinal fluid, pH 7.5). Micrographs were taken of the outside surfaces of the microspheres and of the cleaved microspheres showing their interiors (core). Drug crystals were observed on or near the surface of microspheres prepared from the polymer mixtures, while no drug particles or crystals were seen on the surfaces of microspheres prepared solely from CAB381-20. An acid wash for less than 2?min was capable of extracting all drug on the surface of the microspheres prepared from a mixture of CAB381-20 and cellulose acetate phthalate. The absence of drug crystals on the surface of CAB381-20 microspheres is believed to prevent initial drug release and create a lag time in release profiles. Results suggest that in both microsphere formulations, a layer of drug-free polymer is formed outside the core matrix and is believed to be responsible for the near zero-order release profiles.     

Preparation and in vitro evaluation of propylthiouracil microspheres made of Eudragit RL 100 and cellulose acetate butyrate polymers using the emulsion-solvent evaporation method

The objectives of this investigation are to evaluate the encapsulation efficiency of the anti-thyroid agent 6-n-propyl-2-thiouracil using two polymers of different characteristics (cellulose acetate butyrate polymer, (CAB-551-0.01) and ammonio methacrylate copolymer (Eudragit RL 100) and to study the effect of this encapsulation on the drug release properties. Polymers were used separately and in combination to prepare different microspheres. Also, the effect of polymer solution phase viscosity was studied for each of the polymers and for their combinations. An Ostwald viscometer was used to evaluate the relative viscosities of polymer solution phases and their combinations. Microspheres with 25% theoretical drug loading of 6-n-propyl-2-thiouracil core material were prepared by the emulsion solvent evaporation method. Microspheres prepared from CAB-551-0.01, which has higher relative polymer phase viscosity than Eudragit RL 100, showed significantly lower drug release rates and a noticeable lag time. Polymer combinations of CAB-551-0.01 and Eudragit RL 100 (1:1) showed an interesting synergistic increase in relative polymer solution viscosities at all concentrations. Unlike microspheres prepared from the two polymers separately which follow Higuchi spherical matrix release kinetics, microspheres prepared using a combination (1:1) of the two polymers showed near zero order with faster rates compared to those prepared using CAB-551-0.01 equivalent polymer concentrations. The results of this study suggest that 6-n-propyl-2-thiouracil was successfully and efficiently encapsulated and release rates of matrix microspheres are related to polymer solution phase viscosity, but when polymer combinations were used other factors such as structural effects must be considered.     

Synthesis and characterization of cross-linked chitosan microspheres for drug delivery applications

The present study deals with the synthesis and characterization of cross-linked chitosan microspheres containing an hydrophilic drug, hydroquinone. The microspheres were prepared by the suspension cross-linking method using glutaraldehyde as the cross-linking agent of the polymer matrix. Perfectly spherical cross-linked hydrogel microspheres loaded with hydroquinone were obtained in the size range of 20-100 microm. The effect of the degree of polymer cross-linking, chitosan molecular weight, chitosan concentration and amount of the encapsulated drug on the hydroquinone release kinetics was extensively investigated. It was found that slower drug release rates were obtained from microspheres prepared by using a higher initial concentration of chitosan, a higher molecular weight of chitosan or/and a lower drug concentration. Most importantly, it was shown that the release rate of hydroquinone was mainly controlled by the polymer cross-linking density and, thus, by the degree of swelling of the hydrogel matrix.     

Synthesis and characterization of cross-linked chitosan microspheres for drug delivery applications

The present study deals with the synthesis and characterization of cross-linked chitosan microspheres containing an hydrophilic drug, hydroquinone. The microspheres were prepared by the suspension cross-linking method using glutaraldehyde as the cross-linking agent of the polymer matrix. Perfectly spherical cross-linked hydrogel microspheres loaded with hydroquinone were obtained in the size range of 20–100 μm. The effect of the degree of polymer cross-linking, chitosan molecular weight, chitosan concentration and amount of the encapsulated drug on the hydroquinone release kinetics was extensively investigated. It was found that slower drug release rates were obtained from microspheres prepared by using a higher initial concentration of chitosan, a higher molecular weight of chitosan or/and a lower drug concentration. Most importantly, it was shown that the release rate of hydroquinone was mainly controlled by the polymer cross-linking density and, thus, by the degree of swelling of the hydrogel matrix.     

Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers

Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degrees C) as molecular weight increased from 500 to 10k x g/mol, compared to 25 to 55 degrees C for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release from 30% paclitaxel loaded microspheres in the size range of 50-90 microm was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k x g/mol the amount of drug released from microspheres over 14 days decreased from 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k x g/mol polymer microspheres remained intact.     

聚(ε-己内酯) -聚乙二醇-聚(ε-己内酯)两亲三嵌段共聚物蛋白大分子药物微球的研究

目的:研究以聚(ε-己内酯) -聚乙二醇-聚(ε-己内酯) (PCE)制备蛋白大分子药物微球的方法及其与成品理化性质和释放动力学的关系。方法:采用复乳溶剂挥发法制备牛血清白蛋白(BSA) PCE微球,以扫描电镜观察微球的表面形态,以Mi-croBCA法测定微球载药量和包封率,以累积释放量考察微球体外释药特性。结果:微球外形圆整、表面光滑。不同分子量PCE微球载药量和包封率相近,但体外释药特性显著不同,释放机制为扩散-降解,其中PCE4000因扩散作用释出的蛋白量明显低于其它分子量所制微球。微球体外释药规律符合扩散-溶蚀(Q=k1t1/2+k2t+k3t2+k4t3)(r=0.997)方程。结论:以PCE制备蛋白大分子药物微球具有良好的缓释效果,突释小,释放完全。     

Effects of the permeability characteristics of different polymethacrylates on the pharmaceutical characteristics of verapamil hyhdrochloride-loaded microspheres

Microspheres containing verapamil hydrochloride (VRP) were prepared with various polymethacrylates, with different permeability characteristics (Eudragit RS 100, Eudragit RL 100, Eudragit L 100 and Eudragit L 100-55) and also with mixtures of these polymers in a 1:1 ratio using the solvent evaporation method. The aim was to investigate the effects of the permeability of the polymers on drug release rates and the characteristics of the microspheres. To achieve these aims, yield, incorporation efficiency, particle size and the distribution of microspheres were determined, and the influence of the inner phase viscosities prepared with different polymer and polymer mixtures on particle size and the distribution of microspheres were evaluated. Surface morphologies of microspheres were observed by scanning electron microscope. Drug release rates from microspheres were determined by the half-change method using a flow-through cell. The results indicate that microspheres with different surface morphologies and statistically different yields and incorporation efficiencies could be prepared and their particle size and distribution xariances resulted from the viscosity of the inner phase. Dissolution profiles showed that the drug release rate could be modified depending on the permeability characteristics of polymethacrylates.     

Effects of the permeability characteristics of different polymethacrylates on the pharmaceutical characteristics of verapamil hyhdrochloride-loaded microspheres

Microspheres containing verapamil hydrochloride (VRP) were prepared with various polymethacrylates, with different permeability characteristics (Eudragit RS 100, Eudragit RL 100, Eudragit L 100 and Eudragit L 100-55) and also with mixtures of these polymers in a 1:1 ratio using the solvent evaporation method. The aim was to investigate the effects of the permeability of the polymers on drug release rates and the characteristics of the microspheres. To achieve these aims, yield, incorporation efficiency, particle size and the distribution of microspheres were determined, and the influence of the inner phase viscosities prepared with different polymer and polymer mixtures on particle size and the distribution of microspheres were evaluated. Surface morphologies of microspheres were observed by scanning electron microscope. Drug release rates from microspheres were determined by the half-change method using a flow-through cell. The results indicate that microspheres with different surface morphologies and statistically different yields and incorporation efficiencies could be prepared and their particle size and distribution variances resulted from the viscosity of the inner phase. Dissolution profiles showed that the drug release rate could be modified depending on the permeability characteristics of polymethacrylates.     

PLGA microsphere bioburden evaluation for radiosterilization dose selection

The aim of this study was to determine the bioburden of PLGA microspheres produced by the solvent emulsion/extraction process as a means of determining an appropriate gamma-irradiation dose for sterilization. Bioburden was evaluated on the basis of ISO specifications. The analysis of initial microbial contamination was performed on blank microspheres, prepared by a non-aseptic laboratory scale process. A mean bioburden of 36.04 CFU (colony forming units)/110 mg microspheres was determined. Most of the detected germs originated from human commensal flora. According to the ISO dose-selection method, a gamma-irradiation dose of 19.6 kGy was found sufficient to ensure a sterility level of 10(-6). The effect of the selected irradiation dose on both the molecular weight of the polymer and the kinetics of 5-fluorouracil drug release from the microspheres was compared to the European Pharmacopeia recommended irradiation dose (25 kGy). This 20% reduced dose showed a lower extent of molecular weight reduction of PLGA and a better control of 5-FU release from microparticles. This can be related to reduce polymer radiation damage.     

Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres.

The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules.     

Development and evaluation of stavudine loaded injectable polymeric particulate systems

Present research investigates the formulation of stavudine loaded biodegradable microspheres from different grades of Poly (D, L Lactide-co-glycolide) as a depot system for parenteral delivery. Prolonged release of stavudine facilitates reduction in symptoms of HIV infection and delay AIDS progression by reducing viral load to undetectable levels. Microspheres were prepared from PLGA 85:15 and PLGA 50:50 (RESOMER(?) 505H) by solvent evaporation technique with different drug/polymer ratios (1:4, 1:10, 1:20, 1:50, 1:100) and a polymer solution/vehicle ratio of 1:2. The effects of various formulation variables like polymer type and concentration, surfactant concentration and drug to polymer ratio on the characteristics of microspheres were evaluated. All thirteen formulations of microspheres were evaluated for yield, entrapment efficiency, particle size and In vitro release studies. Microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), residual solvent analysis and confocal laser scanning microscopy (CLSM). Microspheres showed excellent surface topography with uniform distribution and structural integrity of the drug. Resulting microspheres showed the maximum entrapment efficiency of 68.0 ± 1.62% and mean particle diameter below 100μ. Drug release kinetics data were obtained from various kinetic models and best explained by "Higuchi Kinetic" i.e. drug release was largely governed by diffusion through water-filled pores in the matrix. Korsmeyer-Peppas equation depicted that drug release mechanism is anomalous transport, i.e. diffusion as well as polymer relaxation. Drug release from microspheres exhibited the characteristic release pattern of a monolithic matrix system with a maximum of 80-90% drug release in 6-8 weeks demonstrating the feasibility of prolonged delivery of stavudine using biodegradable microspheres for parenteral depot system.     

Chitosan and chondroitin microspheres for oral-administration controlled release of metoclopramide.

This study investigated the usefulness of chitosan and chondroitin sulphate microspheres for controlled release of metoclopramide hydrochloride in oral administration. Microspheres were prepared by spray drying of aqueous polymer dispersions containing the drug and different amounts of formaldehyde as cross-linker. Drug release kinetics were investigated in vitro in media of different pH. Chondroitin sulphate microspheres scarcely retarded drug release, regardless of cross-linker concentration and medium pH, and were thus not further characterized. Chitosan microspheres prepared with more than 15% formaldehyde (w/w with respect to polymer) showed good control release (more than 8 h), and release rates were little affected by medium pH. Release from chitosan microspheres prepared with 20% formaldehyde was independent of pH, suggesting that this may be the most appropriate formulation. The size distribution of the chitosan microparticles was clearly bimodal, with the smaller-diameter subpopulation corresponding to microsphere fragments and other particles. Electron microscopy showed the chitosan microspheres to be almost-spherical, though with shallow invaginations. The kinetics of drug release from chitosan microspheres were best fitted by models originally developed for systems in which release rate is largely governed by rate of diffusion through the matrix.     

Effect of Drug Loading and Molecular Weight of Cellulose Acetate Propionate on the Release Characteristics of Theophylline Microspheres

Microspheres with 40, 50, and 60% drug loading of anhydrous theophylline core material were prepared by the emulsion-solvent evaporation method. Three different molecular weights of cellulose acetate propionate were used as encapsulating polymers. The geometric mean diameter of the microspheres increased with drug loading for all polymers. Dissolution rate for a given particle size fraction also increased with drug loading for all polymers. Higuchi/Baker-Lonsdale spherical matrix dissolution kinetics were followed by narrow particle size fractions of the microspheres. A linear relationship between the T-50% (time required for 50% of the drug to be released) and the square of microsphere diameter was observed with all three molecular weights of the encapsulants. The slowest drug release was obtained with the high molecular weight polymer, which also produced the smoothest microspheres.     

Preparation and control-release kinetics of isosorbide dinitrate microspheres

Microcapsules for sustained release of poorly soluble isosorbide dinitrate (ISDN) were prepared based on ethylcellulose (EC) and/or blended with appropriate amounts of relatively hydrophilic hydroxypropyl cellulose (HPC) as matrix materials using the oil-in-oil emulsion evaporation method. The microspheres studied had three-mode sizes (100-150, 250-300 and 400-450 microm) and four polymer compositions (1, 0.833, 0.67 and 0.5 weight fraction EC). The microspheres were observed to contain essentially no drug crystalline domain and were of a porous morphology. The cumulative amounts of ISDN releasing from the microspheres as functions of mode fractions size and polymer compositions were measured in vitro. It was observed that the microspheres' size influenced the release behaviour of drug more obviously than the polymer composition. The smaller size and the higher hydrophilic HPC content show the faster release rate of drug and the smaller amount of drug residue. The kinetics of drug release depends on the size and polymer composition. The microspheres with 100-150 microm, of all polymer compositions, present one-stage diffusion kinetic with a lag period for drug release. On the other hand, the microspheres with the other two sizes exhibit two-stage diffusion kinetic with a lag period. According to the kinetic model, the microspheres obtained are surmised to have a core-shell like drug concentration distribution and/or a core-shell morphology.     

Ethyl acetate as a dispersing solvent in the production of poly(DL-lactide-co-glycolide) microspheres: effect of process parameters and polymer type

This study deals with the production of poly(DL-lactide-co-glycolide) (PLGA) microspheres using ethyl acetate as a dispersing solvent, a partially water soluble and less toxic solvent, by using emulsification and solvent diffusion/evaporation techniques. PLGA 50 : 50 was used, having molecular weights, 12 000 and 34 000 with the end group capped (RG502, 503) and uncapped (RG502H, 503H) biodegradable polymers. The microspheres were loaded with nifedipine (NFD) as a model drug. Solvent removal from the embryonic microspheres was manipulated by adopting different techniques. These methods have shown a significant effect on the physicochemical and release characteristics of the microspheres. Rapid removal of the solvent resulted in microspheres with a loose matrix and large size. Use of higher molecular weight polymers increased the size of the microspheres as well as delayed release of the drug. The uncapped polymer has given a higher rate of diffusion when compared to the capped polymers. Thermal analyses showed a uniform molecular distribution of the drug in the polymer matrix. The mechanism of drug release from the PLGA microspheres followed the Fickian diffusion.     

Ethyl acetate as a dispersing solvent in the production of poly(DL-lactide-co-glycolide) microspheres: effect of process parameters and polymer type

This study deals with the production of poly(DL-lactide-co-glycolide) (PLGA) microspheres using ethyl acetate as a dispersing solvent, a partially water soluble and less toxic solvent, by using emulsification and solvent diffusion/ evaporation techniques. PLGA 50 : 50 was used, having molecular weights, 12000 and 34000 with the end group capped (RG502, 503) and uncapped (RG502H, 503H) biodegradable polymers. The microspheres were loaded with nifedipine (NFD) as a model drug. Solvent removal from the embryonic microspheres was manipulated by adopting different techniques. These methods have shown a significant effect on the physicochemical and release characteristics of the microspheres. Rapid removal of the solvent resulted in microspheres with a loose matrix and large size. Use of higher molecular weight polymers increased the size of the microspheres as well as delayed release of the drug. The uncapped polymer has given a higher rate of diffusion when compared to the capped polymers. Thermal analyses showed a uniform molecular distribution of the drug in the polymer matrix. The mechanism of drug release from the PLGA microspheres followed the Fickian diffusion.     

Ultrasonic atomization for spray drying: a versatile technique for the preparation of protein loaded biodegradable microspheres

Bovine serum albumin (BDA) loaded microspheres with a spherical shape and smooth surface structure were successfully prepared from poly(lactide-coglycolide) using an ultrasonic nozzle installed in a Niro laboratory spray dryer. Process and formulation parameters were investigated with respect to their influence on microsphere characteristics, such as particle size, loading capacity, and release properties. Preparation of microspheres in yields of more than 50% was achieved using an ultrasonic atomizer connected to a stream of carrier air. Microsphere characteristics could be modified by changing several technological parameters. An increased polymer concentration of the feed generated larger particles with a significantly reduced initial release of the protein. Moreover, microspheres with a smooth surface structure were obtained from the organic polymer solution with the highest viscosity. Microparticles with a low BSA loading showed a large central cavity surrounded by a thin polymer layer in scanning electron microspheres. A high protein loading led to an enlargement of the shell layer, or even to dense particles without any cavities. A continuous in vitro release pattern of BSA was obtained from the particles with low protein loading. Glass transition temperatures (T g) of the microspheres before and after lyophilization did not differ from those of the BSA loaded particles prepared by spray drying with a rotary atomizer. Analysis of the polymer by gel permeation chromatography indicated that ultrasonication had no effect on polymer molecular weight. Molecular weight and polydispersity of the pure polymer, placebo microspheres prepared by spray drying, and placebo microspheres prepared using the ultrasonic nozzle were in the same range. In conclusion, ultrasonic atomization represents a versatile and reliable technique for the production of protein loaded biodegradable microspheres without inducing a degradation of the polymer matrix. Particle characteristics can be modified by adjusting formulation parameters and atomization conditions in a simple manner.     

Ultrasonic atomization for spray drying: a versatile technique for the preparation of protein loaded biodegradable microspheres.

Bovine serum albumin (BDA) loaded microspheres with a spherical shape and smooth surface structure were successfully prepared from poly(lactide-co-glycolide) using an ultrasonic nozzle installed in a Niro laboratory spray dryer. Process and formulation parameters were investigated with respect to their influence on microsphere characteristics, such as particle size, loading capacity, and release properties. Preparation of microspheres in yields of more than 50% was achieved using an ultrasonic atomizer connected to a stream of carrier air. Microsphere characteristics could be modified by changing several technological parameters. An increased polymer concentration of the feed generated larger particles with a significantly reduced initial release of the protein. Moreover, microspheres with a smooth surface structure were obtained from the organic polymer solution with the highest viscosity. Microparticles with a low BSA loading showed a large central cavity surrounded by a thin polymer layer in scanning electron microspheres. A high protein loading led to an enlargement of the shell layer, or even to dense particles without any cavities. A continuous in vitro release pattern of BSA was obtained from the particles with low protein loading. Glass transition temperatures (Tg) of the microspheres before and after lyophilization did not differ from those of the BSA loaded particles prepared by spray drying with a rotary atomizer. Analysis of the polymer by gel permeation chromatography indicated that ultrasonication had no effect on polymer molecular weight. Molecular weight and polydispersity of the pure polymer, placebo microspheres prepared by spray drying, and placebo microspheres prepared using the ultrasonic nozzle were in the same range. In conclusion, ultrasonic atomization represents a versatile and reliable technique for the production of protein loaded biodegradable microspheres without inducing a degradation of the polymer matrix. Particle characteristics can be modified by adjusting formulation parameters and atomization conditions in a simple manner.     

Zero-Order Drug Release from Hydrocolloid Matrices

Matrices are manufactured by direct compression of a powder mixture of a polymer, e.g., methylhydroxypropyl cellulose (MHPC) or polyvinylalcohol (PVAI), and a drug. The following factors that can influence the drug release mode were investigated at constant surface: (i) polymer solution viscosity, glass transition temperature, and swelling; (ii) drug concentration in the matrix and solubility; and (iii) conditions of release experiment (hydrodynamics). In the case of zero-order release profiles (hydrocolloids with low viscosities), only the dissolution of the polymer appears to control the drug release rate. Factors accelerating polymer dissolution resulted in higher release rates. Comparison of swollen and dry hydrocolloid matrices shows that the duration and kinetics of drug release were not controlled by the swelling front moving into the dry polymer, and water penetration and relaxation were not rate controlling. Therefore, the glass transition temperature had no effect on drug release from these hydrocolloids. The higher the hydrodynamic stress exerted on the eroding hydrocolloid, the faster the resulting drug release as a result of accelerated polymer dissolution. With hydrocolloids of very high viscosity the polymer dissolution is slow, and drug relese from the swollen gel appears to be controlled by diffusion according to kinetics of the Higuchi type.