Interfacial cationic polymerization and its application in microencapsulation
Direct polymerization on the solid surfaces of three crystalline biologically active drugs has been carried out in this study to provide a thin polymer film (capsule wall) around the crystals. This polymer film would act as a release controlling layer of the encapsulated crystals into a surrounding fluid. To date there has not been to our knowledge, any study of release control by the encapsulation of solids by direct polymerization. This thesis describes a new technique based on solid/liquid interfacial cationic polymerization which was carried out in an entirely non-aqueous medium to encapsulate solid crystals of almost any size. The first step of the proposed technique involved the adsorption of a surface active agent (α-monoolein) from n-heptane solution onto the surface of the three drug crystals used in this study (KCI, β-estradiol and 5-aminosalicylic acid) to form a hydroxylated (polar) surface which was able to complex an appropriate cationic catalyst, BF₃ (C₂ H₅)₂O from solution to form a highly concentrated layer. This layer was in turn capable of polymerising the appropriate monomers used in this study namely, styrene, 3,4-dihydro-2H-pyran-2-methyl-(3,4-dihydro-2H-pyran-2- carboxylate) (abbreviated to "Cl monomer), 2,3-epoxypropylmethacrylate (GMA) and bisphenol-A diglycidylether (Epikote 828) present in the solution phase to produce the rate controlling polymer layer. Encapsulation processes were also carried out without first adsorbing a surfactant layer onto the crystal surface to investigate whether the surfactant is essential to conduct polymerization and encapsulation of the crystals by a polymer layer. Experiments proved that the encapsulation process took place on the surfaces of the three drugs used in this study even without first adsorbing a surfactant layer on their surfaces. The studies involved measurements of the area per molecule of α-monoolein which recorded an average of 46.1 A/M at air/water interface using the automated Lauda Surface Balance. The specific surface area of each drug powder was measured by nitrogen gas adsorption at low temperature using BET method. Values of 0.074, 3.14 and 1.69 m 2/g were obtained for KC1, β-estradiol and 5-aminosalicylic acid, respectively. The adsorption of α-monoolein on the three drug powders was analyzed using the Lauda Surface Balance, which indicated that KCI had higher affinity towards surfactant adsorption than either β-estradiol or 5-aminosalicylic acid. Encapsulations of the three different drugs by the polymers formed from the four previously mentioned monomers were achieved. Characterization of the polymers, their topographies and permeabilities were carried out using GPC, NMR, FTIR, IR, DSC, SEM, TEM, optical microscopy techniques. From the polymers' analyses and their release profiles, it was found that the C1 and Epikote polymers provided a continuous glassy thin layer which showed potential for release control. Polystyrene provided a microporous brittle layer which did not look practically promising, but interesting signs of tacticity were observed. GMA polymer provided a rubbery porous layer for which further investigation is warranted. The permeability of C1 ploymer layer (0.8% wlw of the total formulation and thickness of 0.11µm) to KCI (very water soluble drug) was found to be 2.5 x 10-¹' cm ²/sec.