SPRAY DRYING AS A PROCESS FOR MICROENCAPSULATION

Abstract

This study investigates the use of spray drying for coating or microencapsulating drug particles (theophylline) with a polymeric material in an aqueous system.

Experiments on operational variables to select a suitable set of conditions were carried out with hydroxypropylmcthylcellulose (HPMC) 50cps. The products were evaluated by their dissolution profiles, flowability and surface characteristics. Results showed that an increase in the air to liquid ratio of the two-fluid nozzle led to a reduction in product particle size and flowability of the product. A higher inlet drying temperature produced particles with improved flowability and a slower drug dissolution rate. The product that was formed at a higher drying air flow rate has better flowability and greater dissolution TSO% values. High feed spray rates resulted in ineffective atomization, producing poorly formed spray dried products and very low product yields. A higher atomizing pressure gave rise to more cohesive and smaller particles with faster drug dissolution.

A solution feed-type produced predominantly polymeric spheres with rod-like drug crystals deposited on the surface. The products of a suspension-feed are microencapsulated drug crystals with fairly smooth surfaces. These encapsulated products showed better flow properties and slower drug release rate. At an optimal polymer concentration, the spherical coated microcapsules formed have better flow properties and slower drug release rate. Deviation from this concentration led to the formation of uncoated or poorly coated particles with fast dissolution rates. Drug release followed a first-order kinetics with HPMC but with sodium carboxymethylcellulose (NaCMC) the release profile followed the Higuchian model. Changes in the composition of the crystal types with increasing NaCMC concentration were also observed. Drug dissolution was faster when the spray dried products had higher drug to polymer ratios. This is due to either incomplete oat formation or the formation of very thin coats. Studies with two viscosity grades of HPMC, 50 and 4000 cps. at various drug to polymer ratios showed the same trend in the dissolution profiles. The optimum drug to polymer ratios for HPMC and NaCMC were found to be 2:1 and 1:1 respectively.

In the studies on the types of plasticizer, concentration of plasticizer and polymer types, films were cast to predict the properties of the coat and characteristics of spray dried products likely to be formed. The presence of different plasticizers affected recrystallization of theophylline in the films. The difference in crystal forms in the films could be related to the drug crystals observed in the spray dried products and in X-ray crystallography studies. Increasing plasticizer content in HPMC films led to the formation of larger crystals and correspondingly larger spray dried products. Cast films that were brittle or badly formed usually resulted in the formation of poorly coated products with rapid drug release. In most instances, observations from films provided a fairly good indication of the spray dried products to be formed.

In the experiments on HPMC (4000 cps) with different plasticizers, spray dried products formed with triethylcitrate consisted of mainly uncoated drug crystals. The coated particles have a porous honey-comb like microcapsule wall, resulting in rapid drug release. Formation of pores due to leaching of the water-soluble plasticizers during dissolution enhanced drug release. The change in the crystal form of theophylline due to the different plasticizers corresponded with the release rate obtained. The dissolution profiles of the spray dried products followed a biphasic first order release kinetics with varying proportion of the ?-and ?-phases. Compared to the products formed without plasticizers, glycerin and citric acid appeared beneficial to microcapsule wall formation, with microcapsules containing citric acid having the slowest drug release. Further investigations with some other carboxylic acids as plasticizers suggested that the low melting point of a plasticizer may be the crucial factor in retarding drug release. The molten state of citric acid during spray drying aided in the cross-linking of the polymer to form a coat more resistant to dissolution thus reducing drug dissolution.

With NaCMC as the coating polymer, the trend in the dissolution T50% values with different plasticizers was similar to that obtained with the HPMC polymer. Citric acid gave rise to products with the most sustained release and a biphasic first-order release kinetics with a predominant ?-pbasc (90%). The spray dried products containing the other plasticizers followed the Hixson Crowell cube root relationship. Structural compatibility between polymer and plasticizer also plays an important role in modifying drug release.

The strength of the cast films has a direct relationship to the dissolution T50% values of the spray dried products with increasing plasticizer concentration. A plasticizer concentration of 30% w/w was found to be suitable for both HPMC and NaCMC.

HPMC acetate succinate, acacia and polyvinyl alcohol were unsuitable for coating by spray drying. Amongst the synthetic celluloses, the trend in dissolution T50% values followed closely to the trend obtained in the moisture uptake studies. Rate of gel formation and erosion appeared to be important determining factors. The slow drug release through NaCMC was attributed in part to a change in drug crystal form. NaCMC showed the best potential as a coating agent as spherical microcapsules were formed.

With the use of co-polymers, HPMC and NaCMC, for coating, the presence of HPMC improved the flowability of the microcapsules compared to those with NaCMC alone. However, the drug dissolution rate was also increased.

The findings have shown that spray drying is a suitable method to prepare microcapsules in a one-step process. The properties of the microcapsules are dependent on the drug, coating polymer and excipients such as plasticizers. By varying any of these formulation factors, the desired microencapsulated product with specific release profiles may be produced.