Amity Institute Of Pharmacy-ndds.docx

AMITY INSTITUTE OF PHARMACY

NOVEL DRUG DELIVERY SYSTEM

CARRIERS FOR DRUG DELIVERY SYSTEM

Submitted by:TANUJA CHAUDHARY B.PHARM (2015-2019) A4513315070

INTRODUCTION

Advancement of new medication particle is costly and tedious. Improving wellbeing adequacy proportion of "old" drugs has been endeavoured utilizing distinctive techniques, for example, individualizing drug treatment, portion titration, and helpful medication checking. Conveying drug at controlled rate, moderate conveyance, directed conveyance are other appealing techniques and have been sought after lively. A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the living body is called a drug. A drug carrier is any substrate used in the process of drug delivery which serves to improve the selectivity, effectiveness, and/or safety of drug administration. The strategy by which a medication is conveyed can significantly affect its viability. A few medications have an ideal focus go inside which greatest advantage is determined, and fixations above or beneath this range can be poisonous or produce no restorative advantage at all. Then again, the moderate advancement in the adequacy of the treatment of serious maladies, has recommended a developing requirement for a multidisciplinary way to deal with the conveyance of therapeutics to focuses in tissues. From this, new thoughts on controlling the pharmacokinetics, pharmacodynamics, non-explicit poisonous quality, immunogenicity, bioacknowledgment, and adequacy of medications were created. These new procedures, frequently called medication conveyance frameworks (DDS), which depend on interdisciplinary methodologies that consolidate polymer science, pharmaceutics, bio-conjugate science, and sub-atomic science. To limit medicate corruption and misfortune, to forestall hurtful reactions and to expand tranquilize bio-accessibility and the division of the medication amassed in the required zone, different medication conveyance and medication focusing on frameworks are as of now a work in progress .Controlled and Novel Drug Delivery which was just a fantasy or, best case scenario plausibility is presently a reality. Amid the most recent decade and half pharmaceutical and different researchers have completed broad and escalated examinations in this field of medication inquire about.

PRODRUG AS A NOVEL APPROACH TO DRUG DELIVERY

The term pro-drug refers to a pharmacologically inactive compound that is converted to an active drug by a metabolic bio-transformation which may occur prior, during and after absorption or at specific target sites within the body. The concept of “pro-drug” was first introduced by Adrian Albert in 1958 to describe compounds that undergo bio-transformation prior to eliciting their pharmacological effect i.e. "therapeutic agents that are inactive but can be transformed into one or more active metabolites." Objectives of Prodrug Design Pharmaceutical objectives:  To improve solubility (e.g., corticosteroids).  To improve chemical stability (e.g., dopamine).  To improve organoleptic properties (e.g., chloramphenicol palmitate is sparingly soluble prodrug of chloramphenicol, which is practically tasteless due to its low aqueous solubility as well as it is hydrolysed to active chloramphenicol by the action of pancreatic lipase).  To decrease irritation and pain. Pharmacokinetic objectives:  To improve oral absorption or permeability and thus increase bioavailability (ampicillin, Epinephrine).  To decrease first pass metabolism (propranolol).  To improve absorption by non-oral routes.  To provide organ or tissue selective delivery of active agent. Pharmacodynamics objectives:  To avoid adverse effects or toxicities.  To mask reactive species to improve its therapeutic index.  To improve site specificity (i.e., that the site of action of an active drug is rather nonspecific such as anticancer agents).

Fig.FATE OF PRODRUG APPROACH

APPLICATIONS OF PRODRUGS: 1. Anticancer agents: Chemotherapeutic agent Paclitaxel was attached to poly (hydroxyl ethyl aspartamide) via a succinic spacer arm by a two-step protocol: synthesis of 2′-O-succinylpaclitaxel; and synthesis of PHEA-2′-Osuccinylpaclitaxel. Investigation carried out using murine myeloid cell line showed that the polymeric prodrug maintains partial pharmacological activity of paclitaxel. The conjugate disappeared from the bloodstream much more quickly as compared to both free drug and naked polymer. 2. In GIT problem:For e.g. sulphasalazine which is formed by coupling of diazotized sulphanilamide pyridine with 5-amino salicylic acid. On oral administration intact sulphasalazine reaches the colon. The azo reductase associated with colonic micro flora convert sulphasalazin to its constituent’s entities, the active species 5ASA available for absorption in colon, while precolonic absorption responsible for side effects is reduced. 3. Immunomodulators: Leflunomide is a novel immunomodulatory agent which exhibits a strong anti-inflammatory action. It is potent therapeutic agent in autoimmune diseases, graft rejection, and tumour therapy. It is isoxazole derivative as a prodrug and is completely converted to its active metabolite which blocks the dihydroorotate dehydrogenase, a key enzyme of the pyrimidine de novo synthesis.

4. Anti-Tubercular agents: Ethambutol (EB), isoniazid (INH) and p-amino salicylic acid (PAS) are potent antitubercular agents having various side effects due to formation of toxic metabolites. Mutual prodrugs of EB with PAS (PE), PAS with PAS (PP) and INH with PAS (PI) were synthesized and characterized. Mutual prodrugs PI and PE significantly eliminate the problem of fast metabolism, toxicity and local irritation and reduction of therapeutic doses.

LIMITATIONS OF PRODRUG DESIGN: As prodrug design has proven highly beneficial in overcoming various undesirable properties of drugs, it can also give rise to a large number of newer difficulties, especially in the assessment of pharmacological, pharmacokinetic, toxicological and clinical properties. Problems at the pharmacological level: These compounds cannot be submitted to preliminary in vitro screening tests like binding studies, reuptake of neurotransmitter and enzyme inhibition measurement because bio activation to their active species is necessary. Problems at the toxicological level: Formation of toxic metabolite, consumption of vital constituent during prodrug activation process, release of a pharmacokinetic modifier which may cause enzyme induction or alter drug excretion are certain toxicity mechanism of prodrug which is not produced by the parent drugs Problems at the pharmacokinetic Studies: The mutual prodrug may not be an ideal substrate for the activating enzymes. Pharmacokinetic studies may lead to numerous misinterpretations. When mutual prodrug and parent molecules are being compared, one must take into account the differences in their respective time courses of action. The maximum activity may appear later for mutual prodrug than for parent compounds, so AUC should be compared as it presents a better criterion for comparison. Problems at the clinical stage: The predictive value of animal experiments is also questionable. The active doses of two mutual prodrugs of the same parent drugs may appear to be same in rats but may be quite different in clinical investigations