Abstract
To evaluate the feasibility of producing solid dispersions with 3-fluid nozzle spray drying to improve the dissolution behavior of lipophilic drugs, 60 experiments were performed based on a Design of Experiment. Solid dispersions with mannitol as a hydrophilic matrix and diazepam as a model drug with a drug load of 20 wt-% were produced. The variables of the experiments were the water/organic solvent ratio, liquid feed flow, total solid content, atomizing airflow and type of organic solvent (ethanol or ethyl acetate). The responses measured were dissolution rate, yield, actual drug load, particle size and crystallinity of diazepam and mannitol. Increasing water/organic solvent ratio was found to be the main factor for enhancing the dissolution rate. The total solid content of the solutions to be spray dried did not affect any of the responses, which means that processing solutions of high concentrations is possible. The choice of organic solvent did not affect the responses as well, i.e. both the fully water miscible solvent ethanol and the poorly water miscible solvent ethyl acetate could be used which makes this production method highly versatile.
Highlights
The majority, even up to 75% [1], of new drug candidates in development pipelines belong to Biopharmaceutical Classification System (BCS) class II [2], having a low solubility in aqueous media
The degree of crystallinity of both components in the solid dispersion can be quantified by DSC because diazepam and mannitol have substantially different melting points, by which their melting endotherms are not overlapping
It was found that a spray drier equipped with a three way nozzle can be used for the production of solid dispersion to improve the dissolution behavior of lipophilic drugs
Summary
The majority, even up to 75% [1], of new drug candidates in development pipelines belong to Biopharmaceutical Classification System (BCS) class II [2], having a low solubility in aqueous media. Due to their low solubility, bioavailability of these drugs is poor after oral administration. It has been shown that bioavailability can be improved by increasing the dissolution rate of the drug [3,4]. There are several formulation strategies to improve dissolution rate, one of them being formulating the drug as a solid dispersion [5]. One of the techniques to produce such solid dispersions is spray drying [8,9]
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