“PRONIOSOMES AS A CARRIER SYSTEM FOR TRANSDERMAL DRUG DELIVERY OF NON- STEROIDAL ANTI-INFLAMMATORY DRUG.”
Brief Resume of Intended Work:
6.1: Need for the Study:
· Non steroidal anti-inflammatory drugs (NSAID) widely used in the treatment of rheumatic diseases. Its oral administration is associated with severe side effects in the gastrointestinal. Transdermal drug delivery have been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. The objectives of this research are to prepare and evaluate anti-inflammatory drug loaded in proniosomes and to perform in vitro drug release properties.
· Anti-inflammatory refers to the property of a substance that reduces inflammation. Anti-inflammatory drugs make up about half of analgesicics remedying pain by reducing inflammation. Anti-inflammatory drugs act by inhibiting cyclooxygenase responsible for the production of prostaglandins in arachidonic acid metabolism. Cyclooxygenase-1 (COX-1) is responsible for the production of prostaglandins. Non-selective inhibition of COX-1 by systemic NSAIDs has been implicated in GI-toxicity. Cyclooxygenase-2 (COX-2) expression, on the other hand, is an inducible mediator of prostaglandin production, and increases dramatically during inflammation and carcinogenesis. Inhibition of COX-2 results in beneficial anti-inflammatory, pain and analgesic affects.
· Drug delivery systems using colloidal particulate carriers such as liposomes, niosomes or proniosomes proved to have distinct advantages over conventional dosage forms with an increasingly important role in drug delivery ;as particles can act as drug containing reservoir, and modification of the particle composition or surface can adjust the drug release rate and/or the affinity for the target site.
· Proniosomes are liquid crystalline-compact niosomal hybrid which could be converted into niosomes upon hydration with water offering a versatile vesicle delivery concept with potential for drug delivery via transdermal route. Upon skin application proniosomes get hydrated with water from skin under occlusion.
ADVANTAGES OF PRONIOSOMES:
1. Both phospholipids and non-ionic surfactants in proniosomes can act as penetration enhancers and help in diffusion of the drug.
2. Proniosomes; provide additional convenience of transportation, distribution, storage and dosing.
3. They are known to avoid many of the problems associated with either the aqueous noisome dispersion, as problems of physical stability like aggregation, fusion and leakage.
4. Proniosomes also avoid problems associated with liposomes like degradation by hydrolysis or oxidation as well as sedimentation, aggregation or fusion during storage.
5. Proniosomes not only offer a promising means of drug delivery, but also could enhance the recovery rate of the skin barrier.
All this make proniosmes;”dry niosomes”, a promising industrial product.1
6.2: Review of literature:
· Proniosomes which are dry formulations of surfactant-coated carrier have been formulated which can be measured out as needed and rehydrated by brief agitation in hot water. Proniosomes were prepared by using spraying method and from the results, it was concluded that Proniosomes derived niosomes represent a promising drug delivery module. They represent a structure similar to liposome and hence they can represent alternative vesicular systems with respect to liposomes, due to the niosome ability to encapsulate different type of drugs within their multi-environmental structure. Proniosomes based niosomes are thoughts to be better candidates drug delivery as compared to liposomes due to various factors like cost and stability.2
· Proniosomal carrier system for captopril is developed for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by encapsulating the drug in various formulations and it is prepared by coacervation-phase separation method. It is evident from this study that proniosomes are a promising prolonged delivery system for captopril and have reasonably good stability characteristics.3
· A new proniosomal delivery system for a poorly water-soluble drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method which consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1: 0.1, respectively.The results reported here indicate that proniosomal capsule formulation can be successfully used to enhance the bioavailability of celecoxib.4
· Aceclofenac proniosomes were prepared, characterized and optimized using central composite design and carry out stability studies. 16 batches of proniosomes were prepared by slurry method and evaluated for the percentage drug entrapment (PDE) and mean volume diameter (MVD) and from this it is evident that the slurry method was found to be simple and suitable for laboratory scale preparation of aceclofenac proniosomes. The statistical approach for optimization of formulation is a useful tool.5
· Controlled release proniosome-derived niosomes were prepared using sucrose stearates as non-ionic biocompatible surfactants for the nebulisable delivery of cromolyn sodium. Conventional niosomes were prepared by a reverse phase evaporation method followed by the preparation of proniosomes by spraying the optimized surfactant–lipid mixture of sucrose stearate, cholesterol and stearylamine in 7:3:0.3 molar ratios onto the surface of spray dried lactose powder. The study has indicated the possibility of manufacturing prolonged release proniosome-derived niosomes as promising drug carriers for the nebulisable delivery of cromolyn sodium. Sucrose stearates was successfully used as non-ionic surfactants in the preparation of niosomal dispersion.6
· Microstructure and transformation of the noisome were prepared from poly(ethylene glycol) (PEG) 6000/Tween 80/Span 80/H2O lamellar liquid crystal (LLC) are studied by the methods of freeze fracture-TEM, negative-staining TEM, dynamic light scattering technique and micro polarity measurements and it is evident that the size of the niosome made from the LLC is lightly larger than that from directly mixing samples. The former niosome is still temporarily and partly held with the LLC microstructure.7
· A proniosome based transdermal drug delivery system of levonorgestrel (LN) were prepared and extensively characterized both In vitro and In vivo. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The system was evaluated In vitro for drug loading, rate of hydration (spontaneity), vesicle size, polydispersity, entrapment. The study demonstrated the utility of proniosomal transdermal patch bearing levonorgestrel for effective contraception. efficiency and drug diffusion across rat skin.8
· Non-ionic surfactant vesicles of frusemide was formulated to enhance its skin permeation and to develop a transdermal therapeutic system using provesicular approach. The effect of various formulation variables on the transdermal flux, amount of drug deposited in skin, and plasma level of drug were studied and the results showed that proniosomal formulation was able to sustain the drug level in the blood and offer a promising means for non-invasive delivery of frusemide. 9
· The feasibility of proniosomes as transdermal drug delivery system for losartan potassium was prepared and different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24hrs. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is 24 hr through rat skin.10
· Piroxicam is a widely used potent non-steroidal anti-inflammatory drug, with due potential for transdermal delivery. Permeation of piroxicam from proniosome based reservoir type transdermal gel formulation across excised rat abdominal skin was investigated using Keshery Chein diffusion cell. There was considerable improvement in flux over the control gel formulation. From this it is evident that Anti-inflammatory studies revealed that proniosome based transdermal drug delivery system of piroxicam was a promising carriers for delivery of piroxicam. There was significant reduction in carrageenan induced rat paw inflammation compared to control.11
6.3 Main objective of the study:
· Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route for NSAIDS and characterization of proniosomes.
7.1 Source of the data:
Data on drugs will be collected from drug information centre, Merck index books physicochemical database and literature search from
Ø Indian institute of Sciences, Bangalore.
Ø Scientific Journals and related articles.
Ø Internet facilities.
Ø Krupanidhi College of Pharmacy library.
Ø Publications and Journals of Pharmaceutics.
7.2 Method of collection of data:
The physicochemical properties of the drug will be collected from drug information center, various standard books, journals, websites and other sources like research literature bases data such as Medline and science direct etc.
The experimental data will be collected from study of the drug; its formulation, through investigation of the process and product variables in the laboratories.
Methods:
· Preparation of proniosomes:
Proniosomes are prepared by accurately weighing ingredients like surfactant mixture, alcohol and drug. All the ingredients are mixed and after mixing it is warmed on a water bath until the surfactants dissolve completely. The aqueous phase was then added and warmed on a water bath till clear solution was formed. The mixture was allowed to cool to room temperature until the dispersion was converted to proniosomal gel12.
· Optimization:
In order to optimize and evaluate various parameters different grades of two types of non-ionic 148 surfactants: Span (sorbitan esters) as Span20, Span60 and Span 149 80, and Tween (polyoxyethylene sorbitanesters) asTween20, Tween 60 and Tween80 were used in addition to cholesterol.
Characterization of Proniosomes:
1. Light microscope
2. Transmission electron microscopy (TEM)
3. Entrapment studies
4. Particle size analysis
5. Assessment of physical stability for proniosomes
6. In vitro release studies
7. Ex vivo permeation studies using rat skin
7.3 Does the study require any investigations or invention to be conducted on patients or
other human or animals? If so, please mention briefly.
Yes, Study requires investigation on animals. The transdermal permeation of the Proniosomes loaded with anti-inflammatory drug will be studied using excised rat skin.
7.4 Has ethical clearance been obtained from your institution in
case of 7.3?
Ethical Committee approval letter is enclosed.
8. LIST OF REFERENCES:
1. Arunothayanun P, Bernard MS, Craig DQM, Ucheghu IF, Fluorence A. The effect of processing variables on the physical characteristics of non-ionic surfactant vesicles (niosomes) formed from hexadecyl diglycerol ether. Int j pharm Res 2000; 201:7-14.
2. Sudhamani T, Priyadarisini N and Radhakrishnan M. Proniosomes Promising Drug Carriers. Int J Pharm Tech Res 2010; 2:1446-54.
3. Gupta A, Kumar SP, Balamurugan M, Mamta singh, Daksha Batia. Design and Development of a Proniosomal Transdermal Drug Delivery System for Captopril. Trop J Pharm Res 2007; 6(2):687-93.
4. Mohamed Nasr. In Vitro and In Vivo Evaluation of Proniosomes Containing Celecoxib for Oral Administration. AAPS Pharm Sci Techol 2010; 11(1):85-89.
5. Solanki A, Parikha J and Parikhb R. Preparation, Characterization Optimization, and Stability Studies of Aceclofenac Proniosomes. Int J Pharm Res 2008; 7(4):237-46.
6. Abd-Elbary A, El-laithy HM and Tadros MI. Sucrose stearate-based proniosome-derived niosomes for the nebulisable delivery of cromolyn sodium. Int j pharm 2008; 357:189–98.
7. Liu T, Guo T. Structure and transformation of the niosome prepared from PEG 6000/Tween 80/Span 80/H2O lamellar liquid crystal. Colloids and Surfaces A: Physicochem Eng Aspects 2007; 295:130–34.
8. Bhavana V, Khopade AJ and Jain NK. Proniosome based transdermal delivery of levonorgestrel for effective contraception. J control Release 1998; 54(2):149-65.
9. AdnanAzeem, NiluJain, ZeenatIqbal, FarhanJalees, Mohammad aqil, sushama talegaonkar. Feasibility of Proniosomes-Based Transdermal Delivery of Frusemide. Phar Dev Technol 2008; 13(2):155-63.
10. Thakur R, Anwer MK and Shams MS. Proniosomal transdermal therapeutic system of losartan potassium. J Drug Target 2009; 17(6):442-49.
11. Chandra A, Sharma PK. Proniosome based drug delivery system of piroxicam. African J Pharm and Pharmacol 2008; 2(9):184-90.
12. Perret S, Golding M, Williams WP. A simple method of preparation of liposomes for pharmaceutical applications and characterizations of liposomes. J Pharm Pharmacol 1991; 43:154-61.