Methods of drug prolong

1. METHODS OF PROLONGING DRUG ACTION
AND DRUG DELIVERY SYSTEMS

2. PROTOCOL
METHODS OF PROLONGING DRUG ACTION:
• INTRODUCTION
• METHODS:
1. RETARDING DRUG ABSORPTION
2. RETARDING DRUG METABOLISM
3. RETARDING RENAL EXCRETION OF THE DRUG
4. INCREASED PROTEIN BINDING
DRUG DELIVERY SYSTEMS:
• INTRODUCTION
• TYPES OF DRUG DELIVERY SYSTEMS
1. CONTROLLED RELEASE DRUG DELIVERY – ORAL AND PARENTERAL
2. BEADED DELIVERY SYSTEMS
3. TARGETED DELIVERY SYSTEMS
4. LOCAL DELIVERY SYSTEMS

3. METHODS OF PROLONGING DRUG ACTION
INTRODUCTION:
 Many drugs may have a short duration of action and may
require frequent administration which may be disturbing and
may result in poor compliance.
 In HTN, DM, TB, EPILEPSY, DEPRESSION AND PSYCHOSIS
prolonged drug action is necessary.
ADVANTAGES :
1. Frequency of drug administration can be ↓
2. It improves patient compliance
3. Large fluctuations in plasma concentration can be avoided
4. Sustained effects can be maintained throughout night

4. Action of drug can be prolonged by various methods
1. RETARDING DRUG ABSORPTION : possible with various routes
• ORAL ROUTE :
Oral absorption of a drug can be retarded by administering it on full stomach or by
pharmaceutical manipulations like slow release/controlled release/ sustained
release / timed disintegration .
e.g. sustained release preparations of nitroglycerine
• TRANSDERMAL / TOPICAL ROUTE:
Drugs impregnated in adhesive patches , straps or as ointments applied on skin.
e.g. pilocarpine ocusert , progestasert , TDP s –scopolamine , nitroglycerine,
clonidine

5. • INJECTABLE ROUTE:
absorption of a drug after parenteral administration can be retarded by:
1. Reduction in the solubility of the drug:
e.g. Benzathine penicillin, procaine penicillin
2. Reduction in the vascularity of the absorbing surface:
e.g. adrenaline with procaine
3. Administering the drug in oily solution
e.g. penicillin with aluminum monostearate
4. Combination of the drug with a protein
e.g. protamine zinc insulin.
5. By esterification
e.g. esterification of testosterone and estrogens with carboxylic acids
6. Pegylation
e.g. interferons

6. 2. RETARDING DRUG METABOLISM:
Less practicable but suitable for only few drugs
Small chemical modification can alter the rate of metabolism without
affecting the biological action
e.g. addition of ethinyl group to estradiol can make it long acting
Inhibition of specific enzymes by one drug can prolong action of another
e.g. carbidopa + levodopa
3. RETARDING RENAL EXCRETION OF THE DRUG:
Tubular secretion of certain compounds can be blocked by adding
compounds which share the same tubular secretory pathway.
e.g. penicillin excretion can be reduced by probenecid
4. INCREASED PROTEIN BINDING OF THE DRUG IN THE PLASMA:
e.g. long – acting sulfonamides sulfamethoxypyridazine

7. Drug delivery systems:
• INTRODUCTION
Drug delivery systems are engineered technologies, for the targeted delivery
and/or controlled release of therapeutic agents to improve its efficacy and safety
.
Drug delivery system controls the rate at which a drug is released and the location
in the body where it is released.
• DEMERITS OF CONVENTIONAL DOSAGE FORMS:
1. Large amount of drug is delivered to the site.
2. Therapeutic concentration is not maintained
3. Repeated dosage is necessary
4. Less patient compliance
5. Fluctuations in concentrations of drugs in blood

8. ADVANTAGES:
1. Delivery of the drug occurs at a controlled rate, slow delivery & targeted delivery can
be achieved.
2. Longer duration of action
3. Bioavailability of the drug ↑
4. ↓ adverse effect
5. ↑ patient compliance
FEATURES OF IDEAL DRUG DELIVERY SYSTEM:
1. Should be inert, biocompatible and mechanically strong
2. Simple to administer and remove
3. Capable of achieving desired drug concentration
4. ↑ the bioavailability of the drug
5. Transport drug intact to site of action avoiding non diseased host tissues
6. Product should be stable, delivery maintained under various physiological variations
7. Should be cost effective

9. Types of delivery systems:
1. Controlled release systems
2. Targeted delivery systems
3. Local delivery systems
CONTROLLED RELEASE SYSTEMS:
1. ORAL:
e.g. osmotic pumps for indomethacin,

10. PARENTERAL :
1. MECHANICAL PUMPS:
E.g. continuous subcutaneous insulin infusion device CSII
Consists of a – insulin reservoir
program chip
keypad
display screen

11. 2. INSULIN JET:
delivers insulin s/c without using needle
e.g. Dermojet insulin
DERMOJET
3. PEN devices:
e.g. Pen insulin

12. 4. Patient controlled analgesia
INFUSION PUMP : 1. Intravenous
2. Epidural
e.g. morphine, fentanyl infusion pump
5. PELLET IMPLANTATION:
e.g. Testosterone

13. PULMONARY DRUG DELIVERY SYSTEMS
The lungs natural ablity to transfer molecules into the bloodstream
has been utilized for delivering drugs to the systemic circulation.
3 types of devices are used:
1. Pressurized metered dose inhaler
2. Nebulizers
MDI
3. Dry powder inhaler
Drugs used are:
-insulin aerosol
-Pentamidine aerosol

14. TARGETED DRUG DELIVERY SYSTEMS
• One of the goals of effective drug delivery is to control and optimize
the localized release of drug at the target site, with minimal non
targeted fraction.
• Hence such drug delivery systems are developed that releases the
drug locally in a highly selective fashion.
• Benefits of such systems are that only a calculated amount of drug is
released at the site of action and there is minimum access to other
sites which can decrease the systemic side effects of the drugs.
These can be grouped into-
1. Nanoparticles

15. NANOPARTICLES:
• Nanoparticles are polymeric particles made of natural or artificial
polymers ranging in size between 10-1000nm
Types: 1. Nanoparticles
2. Nano spheres
3. Nanocapsules

16. NANOERYTHROSOMES DENDRIMER
MODIFIED BUCKYBALL: RADIOTHERAPY

17. 2. LIPOSOMES
• Liposomes are micro particulate lipoidal vesicles that are used as
carriers for the improved delivery of a variety of drugs like
chemotherapeutic agents , imaging agents immunomodulators etc.
• Drugs are encapsulated into the liposomes by encapsulation,
partitioning and reverse loading
• Can be administered I.V, I.M, intra peritoneal and oral routes

18. infectious diseases – amphotericin b (fungal infections and leishmaniosis)
anticancer- doxorubicin in Kaposi’s
malignant tumors , lysosomal storage diseases
AMPHOTERICIN B LIPOSOME

19. IMMUNOLIPOSOMES:
• Immunoliposomes are those in which monoclonal
antibody fragments are conjugated to liposomes
• These are mostly used for molecular targeted drug
delivery
e.g. anti HER2 immunoliposomes loaded with doxorubicin
against HER2 overexpressing tumors

20. POLYMER BASED DRUG DELIVERY SYSTEMS:
• Polymeric micro and nanoparticles are effective carriers that allow
for controlled and targeted drug delivery of small molecules, DNA,
proteins in order to improve the bioavailability of the drug.
• Polymers are usually biodegradable substances
Naturally occurring – collagen, cellulose
Synthetic – polyanhydrides, polyesters, polyacrylic acids,
poly(methyl)methacrylate),
polyurethanes
• Release of drugs are diffusion controlled

22. Polymers are used in
1. Transdermal drug delivery:
e.g. ethyl cellulose T -50 polymer in isosorbide dinitrate TDS
BIO PSA High Tack 7-4301 polymer in trimegestone TDS
2. Oral delivery : polymeric coated (enteric coated)
TDP

23. 3. Parenteral delivery :
e.g. poly(lactide-co-glycolide)PLG for the delivery of diclofenac s/c
4. Dental powder:
e.g. ethyl cellulose strips of tetracycline and metronidazole for local
application in subgingival bacterial infection.
OTHER TARGETED DRUG DELIVERY SYSTEMS
1.MICRONEEDLE ARRAYS :
e.g. vaccine patch

24. LOCAL CONTROLLED DELIVERY SYSTEMS:
1. OCUSERT : pilocarpine for glaucoma
2. PROGESTASERT (IUCD) : hormone releasing
3. DINOPROSTONE VAGINAL INSERT: for cervical ripening
4. IONTOPHORESIS : vasopressin , dexamethasone delivery
5. DRUG ELUTING STENTS: PACLITAXAL, SIROLIMUS

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