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A SEMINAR ON INTRA-NASAL DRUG DELIVERY SYSTEM BY: NALEEN RAJ BHANDARI B-PHARM (2/4) MAHESHWARA INSTITUTE OF PHARMACY CONTENTS INTRODUCTION ADVANTAGES FUNDAMENTAL FACTORS MECHANISMS AND PATHWAYS DELIVERY SYSTEMS ENHANCEMENT IN ABSORPTION APPLICATIONS EXAMPLES CONCLUSIONS REFERENCES INTRODUCTION In ancient times the Indian Ayurvedic system of medicines used nasal route for administration of drug and the process is called as “Nasya” It has been used for local effects extensively in decongestant and local activity. But, in recent times intranasal drug delivery is being considered as a preferred route of drug delivery for systemic bioavailability Various proteins & peptides have shown a good bioavailability Intranasal Drug Delivery System: Advantages Its easy and convenient Can be easily administered to the unconscious patients Compared to oral medications, intranasal medication delivery results in: Faster delivery to the blood stream and higher blood levels No destruction by stomach acid and intestinal enzymes No destruction by hepatic first pass metabolism Compared to IV medications, intranasal medication delivery results in: Comparable blood levels depending on the drug and dose. Fundamental Factors Affecting Nasal Absorption Molecular weight: Absorption of drugs decreases as the molecular weight of drug molecules increases. Mc Martin et al reported a sharp decline in drug absorption having molecular weight greater than 1000Dalton Lipophilicity Drug concentration: Absorption increases as concentration of drug increases. 1-tyrosine shows increased absorption at high concentration in rate.. Particle size: Particle size 10-50 microns adheres best to the nasal mucosa. MECHANISMS Two mechanisms are found to be involved: Fast rate mechanism, which is lipophilicity dependent. Slow rate mechanism, which is dependent on molecular weight. Ex: Nasal delivery of insulin, manitol follows a transport mechanism involving passive diffusion While, absorption of water soluble molecules like sodium cromoglycate take place by diffussion through aqueous pores PATHWAYS Possible drug absorption pathways DELIVERY SYSTEMS Various delivery systems are used like Nasal spray Nose drops Aerosol spray Metered dose nebulizer Saturated cotton pledget The insufflators Mucosal atomizer device (M.A.D) Microspheres ENHANCEMENT IN ABSORPTION Use of absorption enhancers Increase in residence time Administration of drugs in the form of microspheres Various enhancers used Surfactants Phospholipids Chelaters Glycols Cyclodextrins Capable of increasing membrane fluidity and leaching of proteins and lipids from the membrane Applications of Intranasal Drug Delivery Nasal Delivery of Organic based Pharmaceuticals e.g.: Progesterone, Estradiol, Testosterone, Hydralzine, Propranolal, Cocain, Naloxon & Nitrogylcerine. These have shown good Bioavailability by this route. Water-soluble organic based compounds such as Sodium cromoglycate were also found to be well absorbed. Nasal Delivery of Peptide-Based Drugs As peptide based drugs are susceptible to hepatogastrointestinal first pass elimination & instability, they show very low oral bioavailability thus administered through nasal route. EXAMPLES SHOWING DIFFERENT DELIVERY SYSTEMS TRADITIONAL & KURVE’S DELIVERY MUCOSAL AUTOMIZATION DEVICE (M.A.D) EXAMPLES Accuspray from BD Medical– Pharmaceutical Systems is a singleuse nasal sprayer for monodose or bidose administration INTRANASAL Naloxone Conclusions NDDS provides route of drug administration for drugs, which degrade due to first pass metabolism Though it also poses many challenges such as low absorption, toxicological problems, high dose requirements etc.,, thus use of absorption enhancers is proving to be useful increasing the absorption. Insulin is being extensively investigated for its nasal absorption, which may prove a major turnaround in diabetic’s treatment. With ongoing efforts to improve bioavailability of protein and peptide drug through nasal route, the nasal route can become the prime route for administration of protein drugs.. REFERENCES Shaji J and Marathe S.W. NASAL DRUG DELIVERY SYSTEM: OPPORTUNITIES & CHALLENGES INDIAN DRUGS Vol. 45 No. 5 May 2008 Pg no (345 – 353)
