Insoluble Drugs Solid Dispersion by Electrostatic Spray Drying

Situation

Solid dispersions are an efficient means for improving the dissolution rate and hence the bioavailability of a large range of hydrophobic drugs. Oil soluble actives can be delivered in soft capsule but the costs involved are higher than in a tablet.

Challenge

Our goal is to use electrostatic spray drying as a new tool to create a solid dispersion of an oil soluble model drug (Vitamin D3) and to deliver it in an orodispersible tablet (ODT).

Solution

Methods

Vitamin D3 (Vit. D3) solubilized in corn oil at 1 million IU/g and a viscosity of 50 cp at 22 °C (Rapid Visco Analyzer by Perten Instruments) was incorporated in an oil in water emulsion using a pea maltodextrin with a DE17 (KLEPTOSE® Linecaps) as carrier and sodium octenyl succinate starch (CLEARGUM® CO 01) as a surfactant. A stable o/w emulsion of Vitamin D3/ KLEPTOSE® Linecaps/ CLEARGUM® CO 01 was prepared by high speed homogenization (using IKA mixer) followed by high pressure homogenization. The resulting emulsion was atomized through the electrostatic spray nozzle with atomizing gas pressure at 25 psi into PolarDry®’s chamber (Figure 1). The electrostatic nozzle was loaded with 20 kilo-volt charge. Inside the drying chamber, drying gas (90 °C) was delivered at 25 SCFM to support water evaporation. In order to minimize oxidation (keep oxygen level below 5%), the drying gas is a mixture of air and nitrogen gas (Table 1).

Figure 1: PolarDry® 001 / Electrostatic Spray Drying System

Table 1: Electrostatic Spray Drying Process

Results

1) Using electrostatic spray drying, we got a solid dispersion of 212,000 IU/g Vitamin D3 with a narrow particle size distribution of the primary particles and a very good flow of the agglomerated powder in order to compress it (Table 2).

 

Table 2

2) Powder characterization of Vit. D3 electrostatic spray dried solid dispersion parameters (Bulk and tapped density, Carr’s index, water content) are depicted in Table 2.

3) Primary particle size distribution was measured by dynamic light scattering (Malvern Mastersizer 2000) as depicted in Table 2.

4) The agglomerated primary particle morphology was analyzed by SEM (scanning electron microscopy) as in Figure 2.

Figure 2: SEM

 5) Differential scanning calorimetry (DSC) evaluation was carried out on 2920 (TA instrument, Delaware USA) using Universal analysis 2000 software; demonstrating that Vit. D3 was fully encapsulated in the primary particles of solid dispersion by electrostatic spray drying (Figure 3).

 

Figure 3: DSC Thermograms

6) ODT powder formulation (based on PEARLITOL® Flash) loaded with 10000 IU and 1000 IU Vit. D3 (electrostatic spray dried solid dispersion) evaluation (Bulk and Tapped density, Carr’s index , water content) are depicted in Table 3.

 

Table 3: Evaluation of Vitamin D3 ODT Powder Mix

7) 400 mg ODTs loaded with 10000 IU and 1000 IU Vit. D3 were made in a single punch machine (Korsch XP1) and evaluated for hardness, friability and disintegration time (Table 4).

Table 4

Conclusion

Vit. D3 o/w emulsion (formulated with pea maltodextrin with a DE17 (KLEPTOSE® Linecaps) as carrier and sodium octenyl succinate starch ( CLEARGUM® CO 01) as a surfactant was successfully converted by electrostatic spray drying in a solid dispersion with excellent flowability and compressibility. ODTs with very good tabletability were made at 1000 IU and 10000 IU Vit. D3.

References

The information contained in this document is to the best of our knowledge true and accurate, but all instructions, recommendations or suggestions are made without guarantee. Since the conditions of use are beyond our control, we disclaim any liability for loss and/or damage suffered from use of these data or suggestions. Furthermore, no liability is accepted if use of any product in accordance with these data or suggestions infringes any patent. No part of this document may be reproduced by any process without our prior written permission.