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Hybrid insulin cocrystals for controlled release delivery
Mark L Brader1, Muppalla Sukumar, Allen H Pekar
1Bioproduct Pharmaceutical Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. m.brader@lilly.com
Nature Biotechnology
|July 23, 2002
Summary
Researchers developed a novel insulin cocrystal for diabetes therapy. By adjusting the ratio of human insulin and octanoyl-human insulin, drug release rates can be precisely controlled for improved pharmacodynamics.
Area of Science:
- Biochemistry
- Pharmaceutical Sciences
- Drug Delivery
Background:
- Tailoring drug release profiles from formulation matrices offers significant therapeutic benefits.
- Insulin formulations are crucial for managing diabetes, with long-acting options like NPH insulin widely used.
- Controlling insulin pharmacodynamics is key to effective diabetes management.
Purpose of the Study:
- To investigate the cocrystallization of human insulin with a modified insulin derivative (C8-HI).
- To determine if cocrystal composition can modulate in vitro and in vivo drug release rates.
- To identify an optimal cocrystal formulation for basal insulin delivery.
Main Methods:
- Cocrystallization of human insulin and octanoyl-N(epsilon)-LysB29-human insulin (C8-HI) at varying ratios.
- In vitro and in vivo assessment of drug release rates.
- Pharmacodynamic evaluation in somatostatin-treated beagle dogs.
Main Results:
- Human insulin and C8-HI can form cocrystals with tunable release profiles.
- Cocrystal composition directly influences both in vitro and in vivo release rates.
- A 75% C8-HI / 25% human insulin cocrystal demonstrated near-ideal basal pharmacodynamics in dogs.
Conclusions:
- Cocrystallization offers a robust method for modulating insulin pharmacodynamics.
- This approach allows for therapeutic control over drug dissolution while preserving molecular integrity and activity.
- The developed crystalline protein matrix provides a novel strategy for advanced insulin formulation.