Lucy S.C. Wan

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.

Relationship Between Swelling and Drug Release in a Hydrophilic Matrix

AbstractHydroxypropylmethylcellulose (HPMC) is widely used for controlled-release preparations. The process of drug release is controlled by matrix swelling and polymer dissolution. This study examines the mechanism of behaviour of HPMC in a polymer-drug directly-compressed matrix. The results obtained show that the swelling of HPMC which can be described by first-order kinetics is affected by concentration and viscosity grade of the polymer. This swelling action of HPMC in turn is controlled by the rate of water uptake into the matrices. An inverse relationship exists between the drug release rate and matrix swelling rate. This implies that HPMC swelling is one of the factors affecting drug release. The swelling behaviour of HPMC is therefore useful in predicting drug release.

Spheronization conditions on spheroid shape and size

Abstract The effects of Spheronization speed and residence time on the size and sphericity of microcrystalline cellulose (MCC)-lactose spheroids were investigated. Generally, spheroids became larger and more spherical with an increase in the residence time and Spheronization speed. With very high speeds or long residence times, small spheroids resulted. It was found that a combination of speeds ranging from 1000 to 2000 rpm and residence times between 5 and 15 min may be used to produce spheroids with a modal fraction in a size range of 0.7–1.0 mm. The effects of varying MCC content and amount of water required for Spheronization were also studied. The addition of a larger amount of water produced spheroids with larger mass median diameters. A higher proportion of MCC required correspondingly a greater amount of water to form spheroids of a certain mean size. An equation could be used to predict the quantity of water needed to produce spheroids of a required size range. Variation in the particle size of the lactose used also affected the size of spheroids formed. The coarser lactose grade produced larger spheroids. Granule size distribution and sphericity were found to be dependent on the operating conditions. Therefore, with a particular formulation, the variable parameters must be suitably adjusted to complement each other for successful Spheronization.

Chitosan Microspheres Prepared by Emulsification and Ionotropic Gelation

An attempt was made to prepare chitosan microspheres by an emulsion-phase separation technique but without the usual use of glutaraldehyde as a cross-linking agent. Instead, ionotropic gelation was employed in a w/o emulsion. The effect of formulation factors was examined. The results showed that microspheres so formed were spherical, free-flowing, and had smooth surfaces. The rate of addition of counterions was important. Gelation of chitosan droplets should take place before the destabilizing effect of the counterions occurred. This effect is associated with the increase in aqueous phase volume when the counterion solution is incorporated.

The effect of hydroxypropylmethylcellulose on water penetration into a matrix system

Abstract The action of hydroxypropylmethylcellulose (HPMC) on aqueous penetration into matrices containing HPMC of varying viscosity and concentration was studied. The incorporation of HPMC into ibuprofen matrices improved wetting and enhanced water uptake into the matrices. A large volume of water uptake was obtained with a greater amount of HPMC used. A higher molecular weight HPMC has greater intrinsic water uptake property than that of a lower molecular weight. The action of HPMC on aqueous uptake depends on the molecular weight of HPMC. HPMC can be divided into two groups according to its molecular weight. Depending on which group is used in the matrix, increasing the viscosity of HPMC within each group can either increase or decrease the water uptake into the matrices.

Matrix swelling: A simple model describing extent of swelling of HPMC matrices

Abstract The swelling of HPMC matrices was measured by determining the vertical displacement with time using a dial indicator. Curve fitting of the data of swelling was carried out by using the coupled Case I-Case II model. The thickness of the swollen layer formed around the matrix core was greater in HPMC compacts of higher viscosity grade. The rates of Case I (α s coefficient) and Case II (β s coefficient) swelling mechanisms increased with concentration and/or viscosity grade of HPMC.

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.

Heat Treatment of Chitosan Films

AbstractChitosan films, prepared from aqueous solutions of chitosan in 1 % v/v acetic acid, were subjected to heat treatment in an oven at known temperatures for specific durations. The effect of heat treatment on the water resistance of the films was measured by the extent of swelling and dissolution of the films in aqueous media of different pH. The results were correlated to heat induced changes in the physical characteristics of the films. Heat treatment enhanced to a greater extent the water resistance of chitosan films in a medium of low pH than in one of high pH. The improved water resistance may be attributed to the formation of crosslinks and/or crystallites in the films. Both the temperature and duration of heat treatment influenced the degree of heat induced changes in the films.

Spray Drying as a Process for Microencapsulation and the Effect of Different Coating Polymers

AbstractMicroencapsulation of theophylline drug particles was carried out by a spray drying technique using an aqueous system. Comparison was made between the use of a solution and a suspension feed. The spray dried products obtained from a suspension feed were encapsulated and have better flowability. Various polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropylmethylcellulose (HPMC), methylcellulose (MC) and sodium carboxymethylcellulose (NaCMC) were studied to evaluate their spray-coating properties. The results showed that drug release from the coated products was dependent on the hydrophilicity of the polymer. NaCMC, which is more hydrophilic, gelled faster and retarded the drug release more effectively. HPMC and MC produced products with similar dissolution profiles and flow properties. Spray coating with HPMCAS was unsuccessful. The polymers also affect the size and cohesiveness of the products. Smaller size particles which are more cohesive cause agglomeration and delay ...

Surfactant effects on alginate microspheres

Abstract In the production of calcium alginate microspheres involving an emulsification process, the surfactants incorporated can affect the formation of the microspheres. In this study, the influence of the blend of surfactants, hydrophile-lipophile balance (HLB) and the sequence of addition of surfactant on the properties of the microspheres was determined. The findings showed that maintaining the same HLB, surfactants with more fatty acid chains produced larger microspheres which also have higher drug content, whereas for surfactants with longer polyoxyethylene chains, the microspheres were smaller. Varying the HLB, whilst keeping the same blend of surfactants, resulted in changes in the size and shape of the microspheres. The incorporation of the hydrophilic surfactant into the aqueous phase containing the drug gave rise to larger microspheres. These had a lower drug encapsulation efficiency. The drug release rate was faster, and this is attributed to the presence of unencapsulated drug crystals in the product.