Lai Wah Chan

Drug encapsulation in alginate microspheres by emulsification

A method based on an emulsification process was developed for the production of calcium alginate microspheres. Isopropyl alcohol and acetone, which are strong dehydrating agents, were used to aid in the hardening and drying of the microspheres. However, the amount of drug encapsulated was very low. This was due to the drug being soluble in the dehydrating solvents. In the absence of the solvents a high percentage of drug was encapsulated, and this was further increased by forming the microspheres by phase inversion. It was also found that a suspension of the drug particles was required for effective microencapsulation. The efficiency of drug encapsulation generally increased with the ratio of drug to encapsulating material. The microspheres produced were free-flowing and most of them were smaller than 150 microns.

Design of controlled-release solid dosage forms of alginate and chitosan using microwave.

The influence of microwave irradiation on the drug release properties of alginate, alginate-chitosan and chitosan beads was investigated. The beads were prepared with the highest possible concentration of polymer by an extrusion method. Sulphathiazole was selected as a model drug. The beads were subjected to microwave irradiation at various combinations of irradiation power and time. The profiles of drug dissolution, drug content, drug stability, drug polymorphism, drug-polymer interaction, polymer crosslinkage and complexation were determined by dissolution testing, drug content assay, differential scanning calorimetry (DSC) and fourier transform infra-red spectroscopy (FTIR). The chemical stability of the drug entrapped in the beads was unaffected by the microwave irradiation. However, the drug in the chitosan beads underwent polymorphic changes. Polymorphic changes were prevented by means of drug-alginate interaction in alginate and alginate-chitosan beads. Changes in the polymorphic state of drug were found to have insignificant effect on the drug release profiles of chitosan beads. The release-retarding property of alginate and alginate-chitosan beads was significantly enhanced by subjecting the beads to microwave irradiation. Positively charged calcium ions and chitosan are known to interact with negatively charged alginate. DSC and FTIR analyses indicated that the reduction in rate and extent of drug released from the treated beads was primarily due to additional formation of non-ionic bonds, involving alginate crosslinkage and alginate-chitosan complexation. The results showed that microwave technology can be employed in the design of solid dosage forms for controlled-release application without the use of noxious chemical agents.

Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets

The effects of hydroxypropyl methylcellulose (HPMC) of different particle size ranges, size distributions and concentrations on the release behaviour of aspirin from a swellable matrix tablet system were studied. A mean HPMC (Methocel K15M Premium) particle size of 113 microm was identified as a critical threshold in this study. Drug release rate increased markedly when polymer particle size was increased above 113 microm. Release rate was much less sensitive to changes in particle size below 113 microm. Aspirin release mechanism followed first order kinetics where mean HPMC particle size was below 113 microm. Release mechanism deviated from first order kinetics when the mean particle size was above 113 microm. Polymer fractions with similar mean particle size but differing size distribution were also observed to influence drug release rate but not release mechanism. First order release constant K(1) was found to be quantitatively related to the reciprocal of the cube root of both mean polymer particle size and number of polymer particles in the matrix.

Production of alginate microspheres by internal gelation using an emulsification method

Alginate is a natural polysaccharide found in brown algae. Alginates are widely used in the food and pharmaceutical industries and have been employed as a matrix for the entrapment of drugs, macromolecules and biological cells. Alginate microspheres can be produced by the external or internal gelation method using calcium salts. The addition of calcium chloride solution in the final phase of production of microspheres by external gelation method using an emulsification technique causes the disruption of the equilibrium of the system being stirred, resulting in a significant degree of clumping of microspheres. Therefore, in this study, production of alginate microspheres by the internal gelation method using a modified emulsification technique was explored. The influence of calcium salt, added in varying amounts and at different stages, on the morphology of the microspheres was investigated. The effects of other hardening agents and different drying methods were also studied.

Cross-linking mechanisms of calcium and zinc in production of alginate microspheres

Calcium chloride and zinc sulphate were used to cross-link alginate microspheres prepared by an emulsification method. The microspheres cross-linked by a combination of these two salts showed different morphology and slower drug release compared with those cross-linked by the calcium salt alone. From viscosity study, it was found that zinc cations interacted with the alginate molecules to a greater extent than calcium cations. The varying effects of the salts on the properties of the microspheres were largely attributed to their ability to interact with the alginate molecules.

Effect of oil loading on microspheres produced by spray drying

Oil-loaded microspheres were produced by spray drying emulsions consisting of fish oil and modified starch suspensions with different oil loadings. The emulsion stability was assessed by oil droplet size analysis. Microspheres were characterized in terms of size, morphology, yield and microencapsulation efficiency. It was found that an increase in oil loading resulted in emulsions containing larger oil droplets. This corresponded with larger mean microsphere diameters and rounder microspheres. However, high oil loadings produced lower yields and affected microencapsulation efficiencies.

Effects of aldehydes and methods of cross-linking on properties of calcium alginate microspheres prepared by emulsification

Calcium alginate microspheres were prepared by an emulsification method and cross-linked with various aldehydes using different methods. Methanal and pentanedial produced low aggregation of microspheres while octanal and octadecanal produced the opposite effect. The latter two aldehydes displaced very little calcium ions from the alginate microspheres, indicating that the aggregation was due to the tackiness imparted by the aldehydes to the microsphere surface. Higuchis model was not applicable to the drug release from microspheres in this study. The microspheres treated with methanal or pentanedial showed comparable dissolution T75% values which were significantly higher than that of the control. In contrast, octanal and octadecanal produced microspheres with lower dissolution T75% values. The drug contents of the microspheres treated with aldehydes were significantly lower than that of the control. There was insignificant interaction between the aldehydes and the drug. However, the aldehydes were found to impart acidity to the aqueous solution to varying extents, resulting in varying drug loss from the microspheres. The properties of the microspheres were also markedly affected by the method of incorporating the aldehyde. Soaking the microspheres in methanal solution produced microspheres with marked aggregation and low drug content.

Effect of cellulose derivatives on alginate microspheres prepared by emulsification

Generally discrete and spherical calcium alginate microspheres with a high drug encapsulation efficiency were readily prepared by an emulsification process. They were found to release drug rapidly. In the present study, co-polymer in the form of cellulose derivatives was added to sodium alginate in an attempt to modify the drug release profiles of the microspheres. The effects of cellulose derivatives on the morphology and drug encapsulation efficiency of the microspheres were also evaluated. The cellulose derivatives increased the degree of agglomeration of the microspheres. Small and spherical microspheres were produced from cellulose derivatives of low viscosity while larger microspheres which tended to be elongated were produced from cellulose derivatives of high viscosity. The drug encapsulation efficiency and the drug release profiles were influenced by the chemical nature of the cellulose derivative as well as its viscosity. The efficiency of drug encapsulation generally increased while the rate of drug release decreased with increasing viscosity of the cellulose derivatives. Less hydrophilic cellulose derivatives such as methyl cellulose and hydroxypropylmethyl cellulose were found to increase the efficiency of encapsulating sulphaguanidine, while more hydrophilic cellulose derivatives such as hydroxypropyl cellulose and carboxymethyl cellulose had the opposite effect. Among the cellulose derivatives used, only hydroxypropyl cellulose retarded the drug release of the microspheres.

Coating of multiparticulates for sustained release

Multiparticulates are discrete particles that make up a multiple-unit system. They provide many advantages over single-unit systems because of their small size. Studies have shown that multiparticulates are less dependent on gastric emptying, resulting in less inter- and intra-subject variability in gastrointestinal transit time. They are also better distributed and less likely to cause local irritation. The drug dose in a multiple-unit system is divided over the multiparticulates that make up that system. As such, failure of a few units may not be as consequential as failure of a single-unit system.Multiparticulates may be prepared by several methods. Different methods require different processing conditions and produce multiparticulates of distinct qualities. Some of these methods may be broadly classified as pelletization, granulation, spray drying, and spray congealing. Drug particles may be entrapped within the multiparticulates or layered around them. Subsequently, these multiparticulates may be modified in many ways to achieve the desired drug-release profile.One approach to the modification of drug-release profiles in multiparticulates is to coat them. Reasons for the application of coating onto multiparticulates are to obtain functional coats, provide chemical stability, improve physical characteristics, and enhance patient acceptance. Coats are formed from various polymeric coating materials broadly classified as aqueous polymer dispersions, polymer solutions, molten polymers, and dry powders. Depending on the type of coating material used, functions such as sustained release (SR), targeted release, delayed release, and pulsatile release can be achieved. The focus of this review is on SR coating.The most common method used for the application of coating onto multiparticulates is air suspension coating. Other methods include compression coating, solvent evaporation, coacervation, and interfacial complexation. It is also possible to form coated microparticles by spray drying and spray congealing.A major part of this review is focused on factors affecting the coating of multiparticulates and drug-release characteristics from SR coated multiparticulates. Knowledge of these factors is important in the development of SR coated multiparticulates because control of these factors ensures consistency of drug release between batches of multiparticulates. These factors may be classified into four groups: characteristics of cores, characteristics of SR coats, coating equipment, and coating process conditions.

Alginate/starch composites as wall material to achieve microencapsulation with high oil loading

Alginate/starch blends were used as wall material to encapsulate fish oil by spray-drying. The effects of alginate type and content on microsphere morphology, yield and microencapsulation efficiency were investigated. The ability of microspheres to confer protection to the microencapsulated fish oil on storage under stress was also determined. The results showed that the addition of alginate to the wall component resulted in rounder microspheres with higher oil encapsulation efficiencies. Microencapsulated oil was found to be more stable to degradation compared to unencapsulated oil.