Monday, January 25, 2010

DDP 2010: Deliver Drugs When Needed----Controlled Release Design in a Nutshell

Danchen Gao, PhD
Director, New Drug Development
Anchen Pharmaceuticals, Inc

Controlled release dosage forms –
-Administer in high dose at given time
-Repeat dose in several hours

It is independent of the delivery conditions. For sustained release dosage form, the drug will provide a prolonged release. The release rate may be significantly effected by the delivery conditions.

Types of controlled release systems: Oral solid dosage forms (18% of market), Orla liquid dosage forms, depot and liposomes.

Common oral solid controlled release polymeric systems 0 matrix system, reserve system, osmotic pump system

Swellable matrix tablets – incorporate drug into polymer matrix. It’s activated by water penetration, lower glassy rubbery temperature, polymer relaxation and swelling, polymer forms gel layer on tablet surface, polymer and drug dissolution. The gel layer is the key for drug release. It holds drug release rate and prevents matrix discentigration.

Reservoir system – Film coated table or multi-particles. Transport of drug through a network of capillaries filled with dissolution of media. The transport of drug through hydrated swollen film.

Osmotic pump – encased by a semi permeable membrane with an orifice – Water penetrates through the membrane into the tablet core containing osmotic particles and drug. Drug release is via the orifice and controlled by osmotic pressure formed in the tablet. Drug release rate is independent of drug properties and release environment. Offers zero-order release

Oral CR Delivery System Selection
-Drive by market – product differentiation vs. margin. Which stage are you entering into the market? Is it first generation, or extending the patent life of the drug?
-Drive by drug properties – The chemical properties. Is it soluble or insoluble? Is it stable? The ideal can.
-Drive by dose strength – Matrix or coded beas? What is the release profile, it’s easy to adjust the dose. For the matrix tablet, the processing cost is low, but there is a lot of competition.

-Complex an ionic or ionizable drug using ion exchange resigns
-Provide controlled release using polymer coating
-Great for taste masking

Suitable drug candidates:
-Positive change in structure
-Freely soluble in water
-Chemically stable in aqueous conditions
-Has good complexion efficiency
-Prefer with UV absorbance
Example of system that successfully used this – Pennkinetic system

Challenges of the Aqueous Coating Systems –
-Smaller particle size than beads in solid dosage form
-Require hydrophic polymers with high flexibility

Oral Liquid CSR
-Geriatric and pediatric market
-Limited by drug properties and drug loading
-Overcome coating and stability challenges
-In vivo-in vitro correlation

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