advances in monitoring of pharmacotherapeutics and drug delivery system design

1. Advances in Monitoring of
Pharmacotherapeutics and
in Drug Delivery System
Design
ATHAR SHAMIM
M.Pharm, Pharmaceutics
2nd
sem

2. Contents
1. Introduction
2. Definitions
3. Case Study
4. Factors governing pharmacotherapeutics
5. Trends in pharmaceutical product design
6. Advances in drug delivery system design
7. Conclusion

3. 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
Pharmacotherapy

4. 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.

5. Rationale 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.

6. 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.

7. Case Study
Pharmacotherapeutic monitoring for MRSA
Ref: www.pedriatricsupersite.com/view.aspx?rid=83243

8. Advances 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

9. Microscopy imaging methods for ex vivo pulmonary tissues
and pulmonary cellular imaging
Optical Imaging 1. Confocal Microscopy, CM
2. Multiphoton Microscopy, MPM
3. Fluoresence Imaging, FLI and Bioluminescent
Imaging, BLI
Non-optical Imaging 1. Magnetic Resonance Imaging, MRI
2. Computing Tomography, CT
3. Positron Emission Tomography, PET
4. Single Photon Emission Computed Tomography,
SPECT
Multimodal and
Multifunctional
Imaging
1. PET-MRI / PET-CT
2. Confocal Raman Microscopy and Chemical Imaging

11. Schematic of
the instrumental
set up of
confocal
microscopy

13. Factors governing control of drug
concentration at target organ

14. Patient 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.Forgetfulness
2.Confusion or incomplete
understanding of instructions

15. Ways to improve patient
compliance

16. Improving Adherence to drug
therapy – anti HIV

17. Intersubject Variations

18. Control of Drug Release from
Dosage Form

19. 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.

20.  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

21.  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

22.  Increased emphasis on development of new
improved drug delivery systems
 Development of totally new methods of drug
production.

23. Advances in drug delivery
system design

24. 4D Approach for Drug, Delivery,
Design and Development

26. Chronopharmaceutics:
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

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

29. Parentral
chronotherapeutics
infusion pumps (i.e.
Melodie™, Panomat™ V5, Synchromed™,
Rhythmic™) and controlled
release microchip strategies
Orally administered
chronotherapeutics
Contin™, Chronset™, Codas™, Ceform™,
Diffucaps™, TIMERx®, Chronotopic™,
Egalet™, GeoClock™, Port™
Transdermal
chronotherapeutics
ChronoDose™, crystal reservoir [18] and
thermoresponsive membrane systems
Current Status of
chronopharmaceutical drug delivery

30. 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

31.  Ocusert containing pilocarpine used in th
treatment of glaucoma.
 Recombinant DNA technology
 Gene Therapy

32. Prodrug 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.

33.  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.

34. PRODRUG
APPROACH

35. 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.

36.  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

37. 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

38. 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

39. 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

40. Mucoadhesive polymers in buccal delivery
Criteria 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

41. 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/2003/21
543_striant_lbl.pdf).
Buccal mucoadhesive dosage forms for local therapy includes
buccal mucoadhesive tablets containing low dose (10 mg) of an
antifungal drug, miconazole
nitrate.
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

42. 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

43. Recombinant DNA Technology

44. Gene 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).

45.  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.

46. Gene therapy

47. Exploring 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

48. Conclusion
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.

49. References
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

50. References
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

51. Thankyou….