Spray-Dried Dispersion Technology
Bioavailability Enhancement
Spray-Dried Dispersion Technology
Mini Spray Dryer 25mg – 1g
Manufacture
Process Development Toxicology & Early Phase Clinical Supplies
Formulation Identification
Lab Spray Dryer .05mg – 100g
Late Stage Clinical & Commercial
Lab to Pilot Scale 5g – 5kg
Pilot to Commercial 1kg – 0.5Mton
A Proven Technology SDD technology has been proven in thousands of compounds to result in significantly improved bioavailability, typically from three to 15-fold. RE PRESE NTATIV E CLINICA L DATA >1000 Compounds To Date
COMPOUND X Phase III
COMPOUND Y Phase II
200 300 400 0
30
20 15 10 5 0
SDD
A Streamlined Formulation Process
COMPOUND Z Phase I
25
AUC (hr*µg/mL)
100
AUC (hr*µg/mL) SOFT GEL
25 20 15 10 5 0
SDD
CRYSTALLINE
SDD
CRYSTALLINE
RE PRESE NTATIV E PRECLINICA L IN V IVO DATA >550 Compounds To Date
Our approach provides rapid and reliable advancement of low-solubility compounds.
COMPOUND A
COMPOUND B
14 12
AUC (hr*ng/mL)
COMPOUND C
14
14
12
10 8 6 4 2
12
AUC (hr*µg/mL)
Pioneered by Bend Research, the SDD platform incorporates compositions, processes and dosage forms designed and proven to meet performance, stability and manufacturability requirements for a diverse range of compounds. With our integrated product development approach Capsugel can manufacture SDD formulations for all stages of development from preclinical and firstin-human to late-stage development and commercial production. Drug product intermediates based on SDD technology can be formulated into capsules, tablets and other solid dosage forms.
Develop
AUC (hr*µg/mL)
A Flexible Platform
Design
AUC (hr*ng/mL)
Many promising drug candidates have low aqueous solubility, and require enabling technologies and formulations to enhance oral bioavailability. At Capsugel, we know from experience that innovative thinking and flexible approaches are required, along with an array of technologies with which to optimally meet the specific compound characteristics and target product profile. Amorphous solid dispersion using spray-dried dispersions (SDD) is a proven and highly flexible technology approach to improve bioavailability.
10 8 6 4 2
0 CRYSTALLINE
8 6 4 2
0 SDD
10
0 SDD
CRYSTALLINE
SDD
CRYSTALLINE
Spray-Dried Dispersion Technology
C O N C E P T UAL BI OAVAI LABI LI T Y-E N HAN CEMENT T E C HN O LO GY AP P LI CABI LI T Y M AP 100 Crystals Well-Absorbed
Assumes: 100-mg active dose
CRYSTALLINE
10
Compound Aqueous Soluability (mg/ml)
1
INCREASING AQUEOUS SOLUABILITY
Design The first step is understanding your problem statement and clearly defining the target product profile (TPP). Does the compound have low solubility, permeability or a combination of both? We work with you to fully define the characteristics of your compound and offer candidate formulation approaches. The decision to use an amorphous solid dispersion approach such as SDD versus alternate technologies is made based on predictive models and reference maps developed from our experience of advancing thousands of compounds.
0.1
NANOCRYSTALS
0.01 0.001 (µg’S/mL)
AMORPHOUS
0.0001
LIPID/SEDDS Development 0.00001 Starting from the design and TPP, a team of experienced 0.000001 Capsugel scientists and engineers develop the product using (ng’S/mL) a proven roadmap approach. Generally, the formulations 0.0000001 0 1 2 3 4 5 6 7 8 9 10 developed are “phase appropriate” to match the current development phase of the drug candidate. Formulations based INCREASING LIPOPHILICITY on limited data can be used for preclinical or first-in-human stages; later-stage development requires more extensive data and understanding. Capsugel has a full range of pharmaceutical spray dryers, based on proprietary designs, to support early feasibility assessments through clinic studies and commercialization. At each stage of development, we identify the appropriate critical-to-quality attributes and important formulation and process parameters. A robust control strategy is then developed to ensure a quality by design (QbD) approach. Compound Log P
Manufacture Capsugel’s Center of Excellence for solid dispersions in Bend, Oregon (USA) serves a global market with integrated product design, development and manufacturing of pharmaceutical intermediates based on SDD, hot melt extrusion and other enabling technologies. Formerly Bend Research, the site boasts more than 20 years of SDD-based formulation and manufacturing experience, which has resulted in specialized processing techniques and proprietary spray dryer designs. Since advanced dosage form technologies require specialized equipment and infrastructure to manufacture, Capsugel boasts a full range of capabilities to support product development at every phase. Mini spray-drying equipment for feasibility assessments and prototype development with API requirements as low as 100 mg A non-GMP development facility to support rapid product development from early design to clinical manufacture Small- to mid-sized and high-capacity spray-dryers for scale-up, QbD studies and production of toxicology study supplies Commercial scale spray-drying equipment in non-GMP for seamless process development and commercial scale-up to GMP environment GMP production capability for manufacture of registration lots, commercial launch and ongoing supply of drug product intermediate
The Bend site has one of world’s largest high-containment spray dryers for handling potent and highly potent compounds. Learn more about how Capsugel’s Spray-Dried Dispersion Technology can address your bioavailability challenges.
Engineering Medicines To Life
[email protected] Capsugel.com US: 800-845-6973 Europe: + 33 389 205 725
CAPSUGEL WILL USE REASONABLE EFFORTS TO INCLUDE ACCURATE AND UP-TO-DATE INFORMATION ON THIS BROCHURE BUT MAKES NO WARRANTIES OR REPRESENTATIONS OF ANY KIND AS TO ITS ACCURACY OR COMPLETENESS. THE ENTIRE CONTENTS OF THIS BROCHURE ARE SUBJECT TO COPYRIGHT PROTECTION. COPYRIGHT © 2016 CAPSUGEL BELGIUM NV. ALL RIGHTS RESERVED. GMCN 201609004
Challenging Space Few Compounds Observed
Spray-Dried Dispersion Technology
Mini Spray Dryer 25mg – 1g
Manufacture
Process Development Toxicology & Early Phase Clinical Supplies
Formulation Identification
Lab Spray Dryer .05mg – 100g
Late Stage Clinical & Commercial
Lab to Pilot Scale 5g – 5kg
Pilot to Commercial 1kg – 0.5Mton
A Proven Technology SDD technology has been proven in thousands of compounds to result in significantly improved bioavailability, typically from three to 15-fold. RE PRESE NTATIV E CLINICA L DATA >1000 Compounds To Date
COMPOUND X Phase III
COMPOUND Y Phase II
200 300 400 0
30
20 15 10 5 0
SDD
A Streamlined Formulation Process
COMPOUND Z Phase I
25
AUC (hr*µg/mL)
100
AUC (hr*µg/mL) SOFT GEL
25 20 15 10 5 0
SDD
CRYSTALLINE
SDD
CRYSTALLINE
RE PRESE NTATIV E PRECLINICA L IN V IVO DATA >550 Compounds To Date
Our approach provides rapid and reliable advancement of low-solubility compounds.
COMPOUND A
COMPOUND B
14 12
AUC (hr*ng/mL)
COMPOUND C
14
14
12
10 8 6 4 2
12
AUC (hr*µg/mL)
Pioneered by Bend Research, the SDD platform incorporates compositions, processes and dosage forms designed and proven to meet performance, stability and manufacturability requirements for a diverse range of compounds. With our integrated product development approach Capsugel can manufacture SDD formulations for all stages of development from preclinical and firstin-human to late-stage development and commercial production. Drug product intermediates based on SDD technology can be formulated into capsules, tablets and other solid dosage forms.
Develop
AUC (hr*µg/mL)
A Flexible Platform
Design
AUC (hr*ng/mL)
Many promising drug candidates have low aqueous solubility, and require enabling technologies and formulations to enhance oral bioavailability. At Capsugel, we know from experience that innovative thinking and flexible approaches are required, along with an array of technologies with which to optimally meet the specific compound characteristics and target product profile. Amorphous solid dispersion using spray-dried dispersions (SDD) is a proven and highly flexible technology approach to improve bioavailability.
10 8 6 4 2
0 CRYSTALLINE
8 6 4 2
0 SDD
10
0 SDD
CRYSTALLINE
SDD
CRYSTALLINE
Spray-Dried Dispersion Technology
C O N C E P T UAL BI OAVAI LABI LI T Y-E N HAN CEMENT T E C HN O LO GY AP P LI CABI LI T Y M AP 100 Crystals Well-Absorbed
Assumes: 100-mg active dose
CRYSTALLINE
10
Compound Aqueous Soluability (mg/ml)
1
INCREASING AQUEOUS SOLUABILITY
Design The first step is understanding your problem statement and clearly defining the target product profile (TPP). Does the compound have low solubility, permeability or a combination of both? We work with you to fully define the characteristics of your compound and offer candidate formulation approaches. The decision to use an amorphous solid dispersion approach such as SDD versus alternate technologies is made based on predictive models and reference maps developed from our experience of advancing thousands of compounds.
0.1
NANOCRYSTALS
0.01 0.001 (µg’S/mL)
AMORPHOUS
0.0001
LIPID/SEDDS Development 0.00001 Starting from the design and TPP, a team of experienced 0.000001 Capsugel scientists and engineers develop the product using (ng’S/mL) a proven roadmap approach. Generally, the formulations 0.0000001 0 1 2 3 4 5 6 7 8 9 10 developed are “phase appropriate” to match the current development phase of the drug candidate. Formulations based INCREASING LIPOPHILICITY on limited data can be used for preclinical or first-in-human stages; later-stage development requires more extensive data and understanding. Capsugel has a full range of pharmaceutical spray dryers, based on proprietary designs, to support early feasibility assessments through clinic studies and commercialization. At each stage of development, we identify the appropriate critical-to-quality attributes and important formulation and process parameters. A robust control strategy is then developed to ensure a quality by design (QbD) approach. Compound Log P
Manufacture Capsugel’s Center of Excellence for solid dispersions in Bend, Oregon (USA) serves a global market with integrated product design, development and manufacturing of pharmaceutical intermediates based on SDD, hot melt extrusion and other enabling technologies. Formerly Bend Research, the site boasts more than 20 years of SDD-based formulation and manufacturing experience, which has resulted in specialized processing techniques and proprietary spray dryer designs. Since advanced dosage form technologies require specialized equipment and infrastructure to manufacture, Capsugel boasts a full range of capabilities to support product development at every phase. Mini spray-drying equipment for feasibility assessments and prototype development with API requirements as low as 100 mg A non-GMP development facility to support rapid product development from early design to clinical manufacture Small- to mid-sized and high-capacity spray-dryers for scale-up, QbD studies and production of toxicology study supplies Commercial scale spray-drying equipment in non-GMP for seamless process development and commercial scale-up to GMP environment GMP production capability for manufacture of registration lots, commercial launch and ongoing supply of drug product intermediate
The Bend site has one of world’s largest high-containment spray dryers for handling potent and highly potent compounds. Learn more about how Capsugel’s Spray-Dried Dispersion Technology can address your bioavailability challenges.
Engineering Medicines To Life
[email protected] Capsugel.com US: 800-845-6973 Europe: + 33 389 205 725
CAPSUGEL WILL USE REASONABLE EFFORTS TO INCLUDE ACCURATE AND UP-TO-DATE INFORMATION ON THIS BROCHURE BUT MAKES NO WARRANTIES OR REPRESENTATIONS OF ANY KIND AS TO ITS ACCURACY OR COMPLETENESS. THE ENTIRE CONTENTS OF THIS BROCHURE ARE SUBJECT TO COPYRIGHT PROTECTION. COPYRIGHT © 2016 CAPSUGEL BELGIUM NV. ALL RIGHTS RESERVED. GMCN 201609004
Challenging Space Few Compounds Observed
