Advances in Monitoring of Pharmacotherapeutics and

in Drug Delivery System Design

ATHAR SHAMIMM.Pharm, Pharmaceutics

2nd sem

Advances in Monitoring of Pharmacotherapeutics and

in Drug Delivery System Design

ATHAR SHAMIMM.Pharm, Pharmaceutics

2nd sem

Contents

1. Introduction2. Definitions3. Case Study4. Factors governing pharmacotherapeutics5. Trends in pharmaceutical product design6. Advances in drug delivery system design7. Conclusion

Contents

1. Introduction2. Definitions3. Case Study4. Factors governing pharmacotherapeutics5. Trends in pharmaceutical product design6. Advances in drug delivery system design7. Conclusion

Pharmacotherapy is the treatment of disease through the administration of drugs.

Responsible for ensuring the safe, appropriate, and economical use of medicines for direct patient care

PharmacotherapyPharmacotherapy

Need for Monitoring Pharmacotherapy

Need for Monitoring Pharmacotherapy

Ensures proper and rational use of drugs.

Avoid and reduce adverse drug reactions and toxicity.

Maintains drug costs at an optimum level and still provide quality and effective products.

Ensures patient compliance.

Exploits the advances in knowledge made by researchers and scientists.

Rationale use of drugsRationale use of drugs

Rational use of drugs requires that the patients receive medications appropriate to their clinical needs, in doses that meet their own requirement, for an adequate period of time, and at lowest cost to them and their community.

ADVERSE DRUG REACTIONS AND TOXICITY

ADVERSE DRUG REACTIONS AND TOXICITY

The study of ADRs is the concern of the field known as pharmacovigilance.

"A response to a drug which is noxious and unintended, and which occurs at doses normally used… for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function.

Drug toxicity may occur with over dosage of a medication, accumulation of the drug in the body over time or the inability of the patients body to eliminate the drug.

Case StudyCase StudyPharmacotherapeutic monitoring for MRSA

Ref: www.pedriatricsupersite.com/view.aspx?rid=83243

Advances in monitoring of pharmacotherapeuticsAdvances in monitoring of pharmacotherapeutics

Advances in microscopy and complementary imaging techniques to assess the fate of drugs ex vivo in respiratory drug delivery

Reference: C.-W. Park, et al., Advances in microscopy and complementary imaging techniques to assess the fate of drugs ex vivo in respiratory drug delivery, Adv. Drug Deliv. Rev. (2011), doi:10.1016/j.addr.2011.08.004

Microscopy imaging methods for ex vivo pulmonary tissues and pulmonary cellular imaging

Optical Imaging 1. Confocal Microscopy, CM2. Multiphoton Microscopy, MPM3. Fluoresence Imaging, FLI and Bioluminescent

Imaging, BLI

Non-optical Imaging 1. Magnetic Resonance Imaging, MRI2. Computing Tomography, CT3. Positron Emission Tomography, PET4. Single Photon Emission Computed Tomography, SPECT

Multimodal and Multifunctional Imaging

1. PET-MRI / PET-CT2. Confocal Raman Microscopy and Chemical Imaging

Schematic of the instrumental set up of confocal microscopy

Factors governing control of drug concentration at target organFactors governing control of drug concentration at target organ

Patient CompliancePatient Compliance

The major cause of failure of pharmacotherapy is simply that the patient has failed to follow the instructions for the use of medicines. Non-compliance can be due to :1.Forgetfulness2.Confusion or incomplete understanding of instructions

Ways to improve patient complianceWays to improve patient compliance

Improving Adherence to drug therapy – anti HIVImproving Adherence to drug therapy – anti HIV

Intersubject VariationsIntersubject Variations

Control of Drug Release from Dosage FormControl of Drug Release from Dosage Form

Trends in pharmaceutical product design and

production

Trends in pharmaceutical product design and

production More reliance on scientific rather than

intuitive techniques (including preformulation approach to drug product design).

Penicillin by Alexander Fleming.

The psychedelic effects of LSD by Albert Hofmann.

Use of physicochemical methods to improve control over rate and extent of drug release.

Wider use of unit dose products. Development of target oriented dosage

forms.

Greater use of routes of administration other than oral, such as transdermal, ocular, etc

Automation of production operations and use of in-process quality control for total production monitoring

Development of higher speed

pharmaceutical production equipment

Application of optimization procedures to drug product design and manufacture

Use of validation procedures to analyze production operations.

Development of manufacturing methods which are totally environmentally compatible

Increased emphasis on development of

new improved drug delivery systems

Development of totally new methods of drug production.

Advances in drug delivery system designAdvances in drug delivery system design

4D Approach for Drug, Delivery, Design and Development

4D Approach for Drug, Delivery, Design and Development

Chronopharmaceutics: Biological rhythm guided therapyChronopharmaceutics: Biological rhythm guided therapy

“the one size fits all at all times” approach to drug delivery –

Design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration -

Reference: R.B.C Youan, Chronopharmaceutical drug deliv….;Advanced Drug Delivery Reviews 62; 2010; 898-903

Administration-time dependent antihypertensive efficacy of once-a-day nifidipine gastrointestinal formulation

Administration-time dependent antihypertensive efficacy of once-a-day nifidipine gastrointestinal formulation

Parentral chronotherapeutics

infusion pumps (i.e.Melodie™, Panomat™ V5, Synchromed™, Rhythmic™) and controlledrelease microchip strategies

Orally administered chronotherapeutics

Contin™, Chronset™, Codas™, Ceform™,Diffucaps™, TIMERx®, Chronotopic™, Egalet™, GeoClock™, Port™

Transdermal chronotherapeutics

ChronoDose™, crystal reservoir [18] andthermoresponsive membrane systems

Current Status of chronopharmaceutical drug delivery

Current Status of chronopharmaceutical drug delivery

Recent advancements in drug delivery system design

Recent advancements in drug delivery system design

Some advancements in the drug delivery system design are:

Prodrugs such as that of ampicillin etc

Target organ oriented dosage forms such as liposomes, etc

Ocusert containing pilocarpine used in the treatment of glaucoma.

Recombinant DNA technology

Gene Therapy

Prodrug ApproachProdrug Approach

Some recent advances in the prodrug approach used in therapy are:

Antibody-Directed Enzyme Prodrug Therapy (A Promising Approach for a Selective Treatment of Cancer Based on Prodrugs and Monoclonal Antibodies)

5-Aminosalicylic acid 5-Aminosalicylic acid (5-ASA) is an effective

compound to attenuate the inflammatory response in IBD while its mechanism of action is not fully understood.

It usually fails to reach the colon leading to significant adverse effects such as ulcerogenic potential.

Therefore, a prodrug approach for colonic delivery of 5-ASA has become a rational system of drug delivery for the topical treatment of IBD.

PRODRUG APPROACHPRODRUG APPROACH

Targeted drug delivery systems

Targeted drug delivery systems

Some recent advances made in the targeted drug delivery systems are:

Targeted magnetic liposomes loaded with doxorubicin.

Targeting to the hair follicles

Colon targeted drug delivery systems

Cancer targeted drug delivery systems.

i) Targeting, to increase the drug concentration at desired sites of action and reduce systemic levels of the drug and its toxic sequelae in healthy tissues.

(ii) Improved solubility, to facilitate parenteral drug administration.

(iii) Constant rate of drug delivery, resulting in zero-order release kinetics to maintain a constant therapeutic dose at the site of action .

(iv) Reduced clearance, to increase the drug half-life. (v) Increased drug stability, to reduce degradation and

maximize drug action. (vi) Drug delivery across the blood–brain barrier

Goals of a nanoscale drug delivery system

Nanocarrier Drug Disease Advantages

1. SLNs Insulin Diabetes Mellitus

Pulmonary administration possible, increase patient compliance

2. Liposomes Vasoactive Intestinal Peptide-VIP

Hypertension Potential new treatment for hypertension

3. Liposomes or Ambiosomes

Amphotericin B

Fungal infections

Reduced renal toxicity and greater efficacy

4. Gold nanoparticles

Ciprofloxacin Bacterial infections

Sustain release over a no. of hours and great local concentration.

5. PLGA nanoparticles

Rifampicin Tuberculosis Sustain release over a period of days, increase patient compliance

6. SLNs Clozapine Schizophrenia Higher clozapine concentration across BBB

Potential Therapeutic opportunities for nanoscale drug delivery in various diseases

Potential Therapeutic opportunities for nanoscale drug delivery in various diseases

OCUSERT OCUSERT

Pilocarpine ophthalmic (for the eyes) is used to treat glaucoma or ocular hypertension (high pressure inside the eye).

Marketed first by the Alza Corporation.

Common dosage forms are solution, ointments, suspensions, gels, injectables, inserts and orals

Colon targeted drug delivery system Colon targeted drug delivery system oNatural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon.

oVarious major approaches include coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs).

o A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum.

oExample sulfasalazine formulation for Crohn’s disease and Ulcerative Colitis

Mucoadhesive polymers in buccal deliveryMucoadhesive polymers in buccal deliveryCriteria Categories Examples

Source Seminatural/ natural

Synthetic

Agarose, Chitosan, gelatin, gums

Cellulose derivatives- CMC, HPMC

Aqueous solubility Water soluble

Water insoluble

Sodium alginate, CP, HPMC, CMC

Chitosan, EC, PC

Charge Cationic

Anionic

Non ionic

Aminodextran, chitosan, dextran

Sodium alginate, CMC

Hydroxylethyl starch, PVP, PVA

Potential Bioadhesive forces

Covalent

Hydrogen bond

Electrostatic interaction

Cyanoacrylates

Acrylates

Chitosan

Striant is a testosterone buccal system (tablet-like gum patch) recently approved by the United States Food and Drug Administration(FDA). It is indicated for replacement therapy in malesfor conditions associated with a deficiency or absenceof endogenoustestosterone(http://www.fda.gov/cder/foi/label/2003/21543_striant_lbl.pdf).

Buccal mucoadhesive dosage forms for local therapy includes buccal mucoadhesive tablets containing low dose (10 mg) of an antifungal drug, miconazolenitrate.

A promising example of buccal mucoadhesive formulations for systemic use is the buccal delivery of salmon calcitonin (sCT)using thin-film composite containing 40 Ag of sCT

Reference:N. Salamat-Miller et al. , The use of mucoadhesive…./ Advanced Drug Delivery Reviews 57 (2005) 1666–1691

Recombinant DNA Technology

Recombinant DNA Technology

Utilizes isolation and application of restriction endonucleases.

“Human" insulin, the first medicine made via recombinant DNA technology

Insulin was the ideal candidate because

A simple protein and thus easy to copy,

Proved to be safe and effective

Recombinant DNA TechnologyRecombinant DNA Technology

Gene therapyGene therapy

Gene therapy is the insertion of genes into an individual's cells and tissues to treat a disease, such as a hereditary disease in which a deleterious mutant allele is replaced with a functional one.

In 2003 a University of California, Los Angeles research team inserted genes into the brain using liposome's coated in polyethylene glycol (PEG).

The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the blood-brain barrier.

This method has potential for treating Parkinson's disease.

Gene therapyGene therapy

Exploring novel drug delivery systems for ARV drugsExploring novel drug delivery systems for ARV drugs

Ref: E. Ojewole et al., Exploring the use of novel drug delivery systems for antiretroviral drugs, European Journal of Pharmaceutics and Biopharmaceutics 70 (2008) 697–710

ConclusionConclusion

Detailed knowledge of dosage form play important role in pharmacotherapeutics.

New and improved drug delivery systems will lead to safer, more reliable and more effective drug products that further let new capabilities in therapy and a great service to humanity.

ReferencesReferences 1.Gilbert S. Banker and C.T.Rhodes, Modern

Pharmaceutics, Marcel Decker, Advances…., pg 856-869 2.www.pedriatricsupersite.com/view.aspx?rid=83243 3. C.-W. Park, et al., Advances in microscopy and

complementary imaging techniques to assess the fate of drugs ex vivo in respiratory drug delivery, Adv. Drug Deliv. Rev.(2011),doi:10.1016/j.addr.2011.08.004

4.www.popcouncil.org/pdf 5.O.Pillai et al, Drug delivery: an odyssey…,Current

Option in Chemical Biology, 2001 Elsevier,5: 439-446 6. R.B.C Youan, Chronopharmaceutical drug

deliv….;Advanced Drug Delivery Reviews 62; 2010; 898-903

ReferencesReferences

7.Y.Malam et al, Liposomes and nanoparticles: nanosized vehicle for drug delivery in cancer, Trends in Pharmacological Sciences Vol 30, No.11, Elsevier 2009

8.N.Salamat Miller et al, The use of mucoadhesive polymers in buccal delivery, Advance Drug Delivery Reviews 57,2005,1661-1691

9. V.R. Sinha, R. Kumria ,Polysaccharides in colon-specific drug delivery, International Journal of Pharmaceutics 224 (2001) 19–38

10. E. Ojewole et al., Exploring the use of novel drug delivery systems for antiretroviral drugs, European Journal of Pharmaceutics and Biopharmaceutics 70 (2008) 697–710

Thankyou….Thankyou….