Sucrose esters with various hydrophilic-lipophilic properties : novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction

Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System

Development of a multi-unit floating drug delivery system by hot melt coating technique with drug-lipid dispersion

A multi-unit floating drug delivery system containing pellets with lipid coating were fabricated. Coated pellets were prepared by a fluid bed hot melt coating technique with drug-lipid dispersion. Metoprolol tartrate was used as a water soluble model drug and hydrogenated soybean oil (HSO) was used as a lipid carrier. The drug was dispersed in molten HSO and the mixture was directly sprayed on inert nonpareils in a fluid bed chamber. No major interaction between drug and HSO was observed, nevertheless, the drug could be partially dissolved in the molten HSO. Increasing coating amount or adding an inert substance, Aerosil R972, in the coating mixture reduced the initial burst release as well as the total drug release. Increasing drug particle size gave a variation in the drug release due to brittle fracture induced at the nozzle by pressurized atomization air. Coated pellets presented a good floating property in vitro regardless of the coating amount. The present study shows that a drug-lipid dispersion coating prepared by a hot melt coating technique is a promising means for the development of multi-unit floating drug delivery systems

Polymorphic change of a triglyceride base in hot melt coating process and stability acceleration by tempering process

In this study, the influence of hot melt coating condition on polymorphic change of a triglyceride base, hydrogenated soybean oil (HSO) was studied. Metoprolol tartrate was used as a water-soluble model drug. Coated pellets were prepared by spraying drug-lipid dispersion onto nonpareil seeds. A tempering process was employed in order to achieve the stable form of HSO. Differential scanning calorimetry was used to simulate the coating and tempering conditions prior to the processing and to characterize polymorphic change together with powder X-ray diffractometry and hot stage microscopy. Coated pellets possessed three polymorphic forms of HSO but only the stable form was dominant after tempering. Tempered pellets presented crystal growth of HSO with 1-2 mu m microstructure elements. This morphological change led to the reduced porosity and increased surface area of the pellets as well as the increased drug release. The release profile was attributable to the tempering temperature. In order to stabilize the drug release, the tempering process was suggested to perform at the temperature below the melting point of the unstable form

Experimental design and optimization of the hydrogenation process of soybean oil

The hydrogenated soybean oil was prepared by catalytic hydrogenation process in order to be used as a pharmaceutical excipient for hot melt applications. To optimize the hydrogenation process and produce a product whose quality conforms to the hydrogenated vegetable oil type I in the US Pharmacopoeia (USP 24), a central composite design was applied. The influence of three main process parameters, i.e. amount of catalyst, hydrogen pressure and temperature on the hydrogen consumption, the time required for the completion of the reaction and the reaction rate as well as the quality of final products was studied. The increase in the amount of catalyst and temperature significantly enhanced the reaction rate. However, at higher temperature, the acid values of the final products also increased. The thermal behavior of the product showed tolerance to high temperature exposure, i.e. 80-120 degrees C, where unchanged exothermic peaks were determined in the thermograms before and after exposure. This novel excipient is applied in a next step in the hot melt coating application for the preparation of modified release formulations