AAPS-2017 Insoluble Drugs Solid Dispersion by ... · Insoluble Drugs Solid Dispersion by...
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Insoluble Drugs Solid Dispersion by Electrostatic Spray Drying Carmen Popescu 1 , Joseph P Szczap 2 , Joel Migchelbrink 2 1Roquette America, Inc., 2211 Innovation Dr., Geneva, IL, 60134 2 Fluid Air a Division of Spraying Systems Company, 2580 Diehl Road, Aurora, Il 60502 PURPOSE 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. 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 a oral disintegrating tablet (ODT). PURPOSE 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. 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 a oral disintegrating tablet (ODT). METHODS Vitamin D3 ( Vit.D3) solubilized in corn oil at 1million IU/g and a viscosity of 50cp 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 CO01 ® ) as a surfactant. A stable o/w emulsion of Vitamin D3 / Kleptose Linecaps ® / Cleargum CO01 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). CONCLUSIONS Vit D3 o/w emulsion (formulated with pea maltodextrin with a DE17 (Kleptose Linecaps®) as carrier and sodium octenyl succinate starch ( Cleargum CO01®) as a surfactant) was successfully converted by electrostatic spray drying in a solid dispersion with excellent flowability and compressibility properties. ODT with very good tabletability properties were made at 100IU and 10000 IU Vid D3. CONTACT INFORMATION: Carmen Popescu ([email protected]) Joseph Szczap ([email protected] ) Joel Migchelbrink ([email protected]) Poster Number W1036 Moisture content Particle size ( μm) Bulk density Tapped density Carr`s Index Flowability (%) d(0.1) d(0.5) d(0.9) (g/ml) (g/ml) 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 Vit 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 50.4 47.5 N/A Disintegration Time 56 sec 57 sec 1 min 16 sec Friability 0.49 0.69 0.82 Process Parameters Gas flow (SCFM) 25 Inlet Drying Gas Temp °C 90 Atomizing Gas Pressure (psi) 15 Atomizing Gas Temp °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 Figure 1: PolarDry 001 / Electrostatic Spray Drying System Table 1 : Electrostatic Spray Drying Process Parameters 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) . 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. 2.Primary particle size distribution was measured dynamic light scattering Malvern Mastersizer 2000 ) as depicted in Table 2. 3. The agglomerated primary particle morphology was analyzed by SEM (scanning electron microscopy) as in Figure 2. 4. DSC (differential scanning calorimetry evaluation was carried out on 2950 TA instrument, Delaware USA) using Universal analysis 2000 software is demonstrating that Vit D3 is fully encapsulated in the primary particles of solid dispersion by electrostatic spray dried (Figure 3) Table 2 RESULTS 6. 400mg Oral disintegrating tablets ( ODT) Tablets loaded with 1000 IU and 1000 IU Vit. D3 a were made in a single punch machine (Korsh XP1) and evaluated for hardness, friability and disintegration time (Table 4). Figure 2: SEM Figure3 : DSC Thermograms 5. ODT powder formulation (based on PearlitolFlash ® ) loaded with 10000IU and 1000IU Vit. D3 ( electrostatic spray dried solid dispersion ) evaluation (Bulk and Tapped density, Carr’s index , water content) are depicted in Table 3. Vit. D3 ODT Powder Mix 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 Table3 Table 4
Transcript of AAPS-2017 Insoluble Drugs Solid Dispersion by ... · Insoluble Drugs Solid Dispersion by...
Insoluble Drugs Solid Dispersion by Electrostatic Spray DryingCarmen Popescu 1, Joseph P Szczap 2, Joel Migchelbrink 2
1Roquette America, Inc., 2211 Innovation Dr., Geneva, IL, 601342 Fluid Air a Division of Spraying Systems Company, 2580 Diehl Road, Aurora, Il 60502
PURPOSESolid dispersions are an efficient means for improving the
disso lution rate and hence the bioavailability of a large range ofhydrophobic drugs. Oil soluble actives can be delivered in softcapsule but the costs involved are higher than in a tablet. Our goal isto use electrostatic spray drying as a new tool to create a soliddispersion of an oil soluble model drug (Vitamin D3) and to deliver itin a oral disintegrating tablet (ODT).
PURPOSESolid dispersions are an efficient means for improving the
disso lution rate and hence the bioavailability of a large range ofhydrophobic drugs. Oil soluble actives can be delivered in softcapsule but the costs involved are higher than in a tablet. Our goal isto use electrostatic spray drying as a new tool to create a soliddispersion of an oil soluble model drug (Vitamin D3) and to deliver itin a oral disintegrating tablet (ODT).
METHODSVitamin D3 ( Vit.D3) solubilized in corn oil at 1million IU/g and a viscosity of 50cp 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 CO01®) as a surfactant. A stable o/w emulsion of Vitamin D3 / Kleptose Linecaps ®/ Cleargum CO01 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).
CONCLUSIONSVit D3 o/w emulsion (formulated with pea maltodextrin with a DE17 (Kleptose Linecaps®) as carrier and sodium octenyl succinate starch ( Cleargum CO01®) as a surfactant) was successfully converted by electrostatic spray drying in a solid dispersion with excellent flowability and compressibility properties. ODT with very good tabletability properties were made at 100IU and 10000 IU Vid D3.
CONTACT INFORMATION: Carmen Popescu ([email protected]) Joseph Szczap ([email protected] ) Joel Migchelbrink ([email protected])
Poster Numb erW1036
Moisture content Particle size ( µm)
Bulk density
Tapped density
Carr`s Index Flowability
(%) d(0.1) d(0.5) d(0.9) (g/ml) (g/ml)
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
Vit D3 10,000 IU 1000 IUCommercial
1000 IUFc (KN) 11.3 9.8 N/AFe (N) 86 111 N/A
Hardness Average 50.4 47.5 N/A
Disintegration Time 56 sec 57 sec 1 min 16 sec
Friability 0.49 0.69 0.82Process Parameters
Gas flow (SCFM) 25
Inlet Drying Gas Temp °C 90
Atomizing Gas Pressure (psi) 15
Atomizing Gas Temp °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
Figure 1: PolarDry 001 / Electrostatic Spray Drying System
Table 1 : Electrostatic Spray Drying Process Parameters
1.Using electrostatic spray drying we got a solid dispersion of 212,000IU/g Vitamin D3 with a narrow particle size distribution of the primaryparticles and a very good flow of the agglomerated powder in order tocompress it ( Table 2) .2.Powder characterization of Vit. D3 electrostatic spray dried soliddispersion parameters ( Bulk and tapped density, Carr’s index , water content) are depicted in Table 2. 2.Primary particle size distribution was measured dynamic lightscattering Malvern Mastersizer 2000 ) as depicted in Table 2. 3. The agglomerated primary particle morphology was analyzed by SEM(scanning electron microscopy) as in Figure 2.4. DSC (differential scanning calorimetry evaluation was carried out on2950 TA instrument, Delaware USA) using Universal analysis 2000 software is demonstrating that Vit D3 is fully encapsulated in the primary particles of solid dispersion by electrostatic spray dried (Figure 3)
Table 2
RESULTS
6. 400mg Oral disintegrating tablets ( ODT) Tablets loaded with 1000 IU and 1000 IU Vit. D3 a were made in a single punch machine (Korsh XP1)and evaluated for hardness, friability and disintegration time (Table 4).
Figure 2: SEM Figure3 : DSC Thermograms
5. ODT powder formulation (based on PearlitolFlash ®) loaded with10000IU and 1000IU Vit. D3 ( electrostatic spray dried solid dispersion )evaluation (Bulk and Tapped density, Carr’s index , water content) are depicted in Table 3.
Vit. D3 ODT Powder MixTrue
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
Table3
Table 4
