Insoluble Drugs Solid Dispersion by Electrostatic Spray Drying
Case Study

Insoluble Drugs Solid Dispersion by Electrostatic Spray Drying

Authors

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).


fig1

Figure 1: PolarDry® 001 / Electrostatic Spray Drying System

Process Parameters

Gas flow (SCFM)

25

Inlet Drying Gas Temperature (°C)

90

Atomizing Gas Pressure (psi)

15

Atomizing Gas Temperature (°C)

90

MAGNAFLO Pressure (psi)

80

Chamber Pressure (IWC)

-2

Feedstock Flow Rate (mL/min)

10

Voltage Pulse Duration (sec)

3

Voltage Cycle Time (sec)

1

Voltage High (kV)

20

Voltage Low (kV)

1

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).

 

Moisture content (%)

Particle size (μm) 

d(0.1)

Particle size (μm)

d(0.5)

Particle size (μm)

d(0.9)

Bulk density (g/mL)

Tapped density (g/mL)

Carr's Index (%)

Flowability

Batch 1

4.59

9.05

28.59

98.7

0.52

0.56

8

Excellent

Batch 2

4.66

9.18

29.97

141

0.5

0.55

9.5

Excellent

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.
 

fig2

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).

 

fig 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.

 

True density (g/cm3)

Bulk density (g/mL)

Tapped density (g/mL)

Carr's index (%)

Flow

1000 IU

1.485

0.557

0.625

10.88

Good

10000 IU

1.4651

0.512

0.581

11.88

Good

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).

Vitamin D3

10,000 IU

1000 IU

Commercial 1000 IU

Fc (kN)

11.3

9.8

N/A

Fe (N)

86

111

N/A

Hardness Average (N)

50.4

47.5

N/A

Disintegration Time

56 seconds

57 seconds

1 minute 16 seconds

Friability (%)

0.49

0.69

0.82

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

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