Drug delivery system :Drug delivery system Controlled release system AMIT M. GUPTA LECTURER, AGNIHOTRI COLLEGE OF PHARMACY, WARDHA


Sustained drug delivery system :Sustained drug delivery system Simply prolong the drug release Plasma drug level for extended period of time Not necessarily at predetermined time rate Reduce dosing frequency Uniform plasma concentration at steady–state.


Controlled drug delivery system :Controlled drug delivery system Prolonged release, Delivers the drug at predetermined rate, locally or systemically for specified period of time.


Pharmaceutical dosage forms for systemic administration :Pharmaceutical dosage forms for systemic administration Generations of dosage forms 1st gen. – conventional (unmodified) release of API 2nd gen. – controlled release of API (CR) 3rd gen. – targeted distribution drug delivery systems


Conventional vs. Controlled release dosage forms :Conventional vs. Controlled release dosage forms I. Gen. – disintegration (? desegregation) of the dosage form and dissolution of is spontaneous process; drug absorption and distribution is based only on physico-chemical properties. II. Gen. The release is under control of the drug delivery system Advantages: Avoids fluctuations of plasma drug concentration ? better safety and efficacy Decreased frequency of drug administration (often once daily admin) ? better compliance May overcome some problems with BAV Can be much more economical (better cost-effectiveness) Sustained release (SR) – release of the initial API dose & further prolonged release Controlled release (CR) – properly controlled (0. order) release


Biopharmaceutical consideration :Biopharmaceutical consideration Rate limiting step of controlled release Rate limiting step of conventional release 1. Release from formulation2. Movement within body during its passage to site of action


Biopharmaceutical properties :Biopharmaceutical properties Molecular weight of drug Aqueous solubility of the drug Apparent partition coefficient of drug Drug pKa and pH Drug stability in G.I.T. Mechanism of absorption Route of administration


Pharmacokinetic characteristics of drug :Pharmacokinetic characteristics of drug Absorption rate Elimination half-life Rate of metabolism Dosage form index (DI), (plasma peak-valley ratio i.e. Css.max to Css.min.)


Pharmacodynamic characteristics of drug :Pharmacodynamic characteristics of drug Therapeutic range Therapeutic index Plasma concentration- Response relationship


Drug release patterns :Drug release patterns Drug disposition fallows first order kinetics Rate limiting step is in the absorptions rate of drug release Drug release rapidly and completely absorbed


Approaches :Approaches A. Continuous release system Dissolution Controlled drug release system a. Matrix Dissolution Controlled system b. Encapsulation/coating Dissolution Controlled drug release system 2. Diffusion Controlled drug release system a. Matrix Diffusion system b. Reservoir devices 3. Dissolution and diffusion Controlled drug release system 4. Ion exchange resin drug complexes 5. Slow dissolving salts and complexes 6. pH depending formulation 7. Osmotic pressure Controlled system 8. Hydrodynamic pressure Controlled system


Dosage forms for systemic administrationParenteral route dosage forms :Implants Controlled drug delivery for over a long time (months/years) Principle Reservoir (Osmotic/diffusion) systems Matrix systems Non-biodegradable Biodegrable polymeric materials with dispersed drug Advantages – largely overcomes problems with individual compliance Disadvantages – mini-surgery is needed, uneasy to simply discontinue the therapy, local reactions Examples: hormones/contraception Dosage forms for systemic administrationParenteral route dosage forms


Dosage forms for systemic administration Transdermal drug delivery sytems (TDDS) :Dosage forms for systemic administration Transdermal drug delivery sytems (TDDS) Advantages Elegant alternative to injectables Pain and stress-free No need for trained specialist Long-term drug delivery with minimal fluctuations of drug concentrations Good compliance Unlike other controlled drug delivery systems, the delivery of the API can be immediately discontinued (e.g., upon occurrence of adverse reactions…) Disadvantages Not feasible for all API ! Mr < 500 Well balanced lipohilicity High potency (high doses can not be accommodated and delivered) ? Penetration enhancers can help! Local relations (irritation, disruption of barrier skin function) Need not be practical/comfortable Need not be cost-effective Examples of clinical use: hormones (HRT, contraceptives), opioid analgesics (e.g., fentanyl), nitroglycerine, nicotine (RT), clonidine or scopolamine


Delayed transit and continuous release system :Delayed transit and continuous release system Altered density system a. high density pellets b. low density pellets Mucoadhesive system Size based system


Delayed release system :Delayed release system Intestinal release system Colonic release system


Parenteral Controlled release system :Parenteral Controlled release system Injectabales Solutions Dispersions Microsphers and microcapsules Nanoparticals and niosomes Liposomes Resealed erythrocytes B. Implants devices Osmotic pumps Vapor pressure powered pumps Battery power pumps


Transdermal drug delivery system :Transdermal drug delivery system Matrix Reservoir Mixed Reservoir


Ophthalmic drug delivery system :Ophthalmic drug delivery system Inserts or ocuserts Intravaginal and intrauterine drug delivery system


Liposome's :Liposome's


Niosomes :Niosomes


In vitro measurements of drug availabilityIn vivo measurements of drug availability :In vitro measurements of drug availabilityIn vivo measurements of drug availability Evaluation testing


Thank you for your attention :Thank you for your attention