Advantages :- Reduces frequency of adm -more convenient Improves patient compliance- single morning dose can’t be forgotten than a 6 or 8hly regimen (multiple dosing). Quarterly administered contraceptive over one that has take daily. Avoids large Plasma fluctuations. Maintains drug effect for the whole day/night. e.g.. Antiasthmatics & anticonvulsants. Drugs need not to be made long acting-
Drugs with brief therapeutic effect-hypnotics &
head ache remedy.
Drugs with long duration- doxycyclin, omeprazole,
digoxin & amlodipine.
Drugs with longer t1/2 > 12hr- no need of C.R.F.
C.R.F=controlled release formulation .
Methods to be used for prolongation of a drug:
By Retarding drug absorption.
By Retarding drug metabolism in the liver.
By Retarding drug excretion.
By using drugs of highly protein bound.
By modifying the molecular structure of a drug.
1. Retarding drug absorption. a. Oral Route:- Administration of drugs on full stomach. Sustained Release Tablets & Spansules. -Drugs particles are coated with resins, plastic materials or other Substances - active ingredients released slowly into G.I.T. Controlled Release Tab/Cap- -semipermeable membrane control the release of active drug from dosage form. -prolongs actions by 4 to 8hrs & safely reaches the colon. - drug release pattern & maintenance of plasma levels are different with normal Tab/cap. b)Parenteral Route– 1. By decreasing the vascularity of absorbing surface. e.g. Adrenaline + lignocaine/procaine. 2.By decreasing the solubility of drug. E.g. penicillin + procaine(poor H2O soluble solvent)& Benzocaine 3.Administration of drug in oily solution/bees wax. E.g. penicillin + aluminum monosterate (H2O repellant) Pitressin tannate in oil. 4.Combining a drug with protein. E.g. Protamine zinc insulin 5. Esterification:-(benzoate,enanthate,propionate) Steroidal Sex Hormones are esterified with carboxylic acid which are absorbed slowly. 6.Pegylation: Combined with poly ethylene glycol 7.Depot Preparation: e.g. Long acting Progesterone-contraceptive, DOCA- Addison's disease. c) Dermal Route:- 1.Pellet implantation -desoxycorticosterone acetate (DOCA) 2.Sialistic and biodegradable implants (Norplant)-oestrogens. 3.Transdermal System- GTN ointment, Transdermal disc’s, Patches(estradiol, scopolamine, corticosteroids) d) Eye- Ocuserts e.g. pilocarpine for glaucoma 2) Retarding drug metabolism: Hepatic Microsomal Enzyme system-biotransformation
Enzyme inhibitors- inhibits metabolism of certain drugs.
E.g.
1. Allopurinol inhibits the degradation of 6-MP.
2.Ritonavir boosts the levels of Indinavir.
3.Cilastatin protects Imipinem from degradation in
3.Retarding renal excretion:- Excretion of drugs by G.F can't be blocked/slowed.
Tubular secretion of drugs is an active process can be
blocked by competing substance/drugs. E.g. Ampicillin Penicillin, Probenecid(blocks OAT) cephalosporin's, Tubular lumen sulfa drugs urine
Mtx & Indomethacin penicillin
OAT Probenecid 4) By increasing protein binding in plasma-
Drug congeners are prepared with high plasma protein
binding from which active drug is slowly released.
Long acting sulfonamide- sulfamethoxypyridazine
,sulfodoxin
-highly bound to plasma proteins.
Short acting sulfonamide- sulfadiazine.
-less bound to plasma proteins.
Suramin used to RX Trypanosomiasis-
-highly bound to plasma proteins.
Ptn bounded drug acts as a- Drug acceptors Drug reservoir Pharmacologically inactive Prolongs drug duration Drug remains in vascular compartment(can’t diffuse thru’ membranes) aVd is low(<5L) Delays drug metabolism Delays drug excretion Decreases drug clearance & can’t be removed by hemodialysis. Diminishes drug penetration into CNS. Responsible for drug displacement interactions(toxicity) Attains less conc. In ISF, CSF, tissues-therapeutic activity is low. E.g- long acting sulfonamides used to Rx diseases 5) Drugs sequestered in adipose tissue-
e.g. Quinestrol - cyclopentyl ester of estradiol have prolonged
drug action. 6) By modifying the molecular structure of a drug-(SAR) e.g. Procaine is L.A- on I.V route adm- - reduces cardiac rate & excitability - but rapidly hydrolyzed - hence cardiac action is too transient. Procainamide - structurally similar to Procaine - Resistance to hydrolysis, - Longer acting RX cardiac arrhythmias. SAR-Structure activity relationship. PROCESSES METHODS EXAMPLES
peptidase inhibitors -Cilastin prolongs action of Imipenem Excretion Competition for same -Probenecid prolongs action transporters for T.Secretion of penicillin/ampicillin. THANK YOU @$!#*
Method Development and Validation of Simultaneous Estimation of Etofylline, Theophylline and Montelukast in Bulk and Tablet Dosage Form by First Order Derivative UV Spectrophotometric Method
International Journal of Innovative Science and Research Technology