Microsoft word - 2

Research Article [Kumar et al., 4(7): July, 2013]
CODEN (USA): IJPLCP ISSN: 0976-7126
INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES Formulation and evaluation of sustained released niosomes P. Aravinth Kumar*, Ranjit Singh, K. Karthick and K.S.G. Arulkumaran
KMCH College of Pharmacy, Coimbatore, (Tamilnadu) - India Abstract
The main objective of the present study was to encapsulate Pregabalin in niosomes for achieving prolonged release & longer duration of action. Niosomes containing Pregabalin was formulated using two surfactants such as span 40 & span 60 and evaluated for various parameters. The microscopic examination of the prepared niosomes revealed spherical small unilamellar vesicles of 80-120 nm and 250- 280 nm for F I and F II. Invitro release studies showed that the percentage amount of free drug released was 99.04% within 2.5 hours. FI showed 84.99 % of drug release within 19 hours. F II showed 93.48 % of drug release within 20 hours. Storage under refrigerated condition showed greater stability with 97.23% of drug content at the end of 3 months. Key-Words: Pregabalin, Epilepsy, Niosomes, Thin film hydration method, Invitro release Introduction
Epilepsy is a common chronic neurological disorder Niosomes are non-ionic surfactant vesicles obtained on that is characterized by recurrent unprovoked seizures. hydration of synthetic nonionic surfactants, with or These seizures are transient signs and / or symptoms without incorporation of cholesterol or other lipids2. due to abnormal, excessive or synchronous neuronal They are vesicular systems similar to liposomes that activity in the brain1. About 50 million people can be used as carriers of amphiphilic and lipophilic worldwide have epilepsy at any one time. Epilepsy is drugs. Niosomes are promising vehicle for drug usually controlled, but not cured, with medication, delivery and being non-ionic, it is less toxic and although surgery may be considered in difficult cases. improves the therapeutic index of drug by restricting its However, over 30% of people with epilepsy do not action to target cells. In niosomes, the vesicles forming have seizure control even with the best available amphiphilic is a non-ionic surfactant such as Span 60 medications. Not all epilepsy syndromes are lifelong which is usually stabilized by addition of cholesterol some forms are confined to particular stages of and small amount of anionic surfactant such as dicetyl childhood1. Epilepsy should not be understood as a phosphate3. Niosomes have been used to prolong the single disorder, but rather as a group of syndromes circulation of the drugs, to alter the distribution of with vastly divergent symptoms but all involving drugs and they offer a host of other advantages. episodic abnormal electrical activity in the brain. Niosomes favour selective delivery of drugs and Pregabalin is one of the most effective drug in the improves the therapeutic efficacy and reduces the treatment of epilepsy, it is an ideal second generation severity of side effects. The need for present study is to Anti Epileptic Drug (AED) that eliminates seizures encapsulate the drug in the niosomes vesicles for effective central nervous system drug delivery for a prolonged period of time. Thus the present studies deals with preparation methods, characterizations, * Corresponding Author
factors affecting release kinetic, advantages, and E.mail: [email protected] applications of niosomes.
Advantages of niosomes
The first report of non-ionic surfactant vesicles came from the cosmetic applications devised The application of vesicular (lipid vesicles and non-ionic surfactant vesicles) systems in Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 4, Issue 7: July: 2013, 2770-2774
Research Article [Kumar et al., 4(7): July, 2013]
CODEN (USA): IJPLCP ISSN: 0976-7126
cosmetics and for therapeutic purpose may The niosomes vesicles containing were subsequently formed. The suspension was then sonicated to form The vesicle suspension is water–based vehicle. Characterization of niosomes
Invitro Release Studies5
They possess an infrastructure consisting of The in vitro releases of niosomes were studied by using simple diffusion cell apparatus. The diffusion cell apparatus consists of a glass tube with an inner diameter of 2.5 cm, open at both ends, one end of the tube is tied with Sigma dialysis membrane, which The characteristics of the vesicle formulation serves as a donor compartment. Niosomes equivalent are variable and controllable. Altering vesicle to 5 mg of Pregabalin was taken in a dialysis tube and composition, size, lamellarity, tapped volume, placed in 200 ml of water. The medium was stirred by surface charge and concentration can control using the magnetic stirrer and the temperature was maintained at 37±20C. Periodically 5ml of samples The vesicles may act as a depot, releasing the were withdrawn and after each withdrawal same volume of medium was replaced. Then the samples They are osmotically active and stable, as well were assayed spectrophotometrically at 215 nm using as they increase the stability of entrapped drug. They improve oral bioavailability of poorly Determination of Drug Entrapment Efficiency5-7
absorbed drugs and enhance skin penetration of 1 ml of the sample is taken and centrifuged at 13000 RPM at 40C for 90 minutes using eppendorf centrifuge. Supernatant was separated without disturbing the Niosomal dispersion in an aqueous phase can supernatant layer (free drug) was diluted using PBS pH 7.4 and analysed using UV spectrophotometer. administer normal vesicle in external non- %drug entrapment=-------------------------------- X 100 Material and Methods
Materials
Scanning Electron Microscopy5-7
Pregabalin was a gift sample from Micro Labs (Hosur), Niosomes were characterized by SEM (JEOL). Cholesterol was purchased from Qualigens Fine Niosomes containing Pregabalin was taken in a cover Chemicals (Mumbai), Span 40 and Span 60 was glass and transferred on a specimen stub. Dried obtained from Kemphasol, all other reagents were of samples were coated with platinum alloy to a thickness of 100 A using a sputter coater. After coating, scanning Preparation of Niosomes4
Pregabalin niosomes were prepared by Thin Film Particle Size Distribution5-7
Hydration Technique using Rotary flash Evaporator. The size of the formulation was analyzed by using a The formulation code and ingredients are given in the Zetasizer, Ver. 601 (Malvern Instrument Ltd). The Table 1. According to this method, accurately weighed formulation was placed in the sample holder and the quantity of cholesterol and non-ionic surfactant were dissolved in 10 ml of chloroform and poured into a Stability Studies5-7
round bottom flask. The flask was rotated at 1.5 cm The formulated niosomes were subjected for stability above a water bath at 60oC± 20C under reduced studies for a period of three months. The formulated pressure, until all the organic phase evaporated and a niosomes were divided into 3 portions. First portion thin layer was formed on the wall of a round bottom was kept at refrigeration (40C±10C) temperature. flask. Then accurately weighed quantity of drug was Second portion was kept at room temperature. Third dissolved in 10 ml of water. The dried non- ionic portion was kept at 400C±20C, 70% ±5 %. surfactant and cholesterol film was subsequently Results and Discussion
hydrated with this drug solution and the mixture was The SEM analysis of the prepared niosomes revealed rotated by immersing in a water bath at 60oC± 20C for spherical small unilamellar vesicles of 80-120 nm and 1 hour until a good dispersion of mixture was obtained. 250- 280 nm for F I and F II (Figure 1 & 2). These Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 4, Issue 7: July: 2013, 2770-2774
Research Article [Kumar et al., 4(7): July, 2013]
CODEN (USA): IJPLCP ISSN: 0976-7126
results revealed that the vesicle diameter complies Acknowledgement
within the niosomal size range of 100-300 nm (Table The authors are thankful to the Principal Dr. A. 2). The entrapment efficiency of drug in F II containing Rajasekaran, KMCH College of Pharmacy for span 60 was found to be 66.50% (Table 2) which providing the necessary facilities in the College, showed maximum percent drug entrapment where as Sincerely thanks to Mr. K Selvaraj, Assistant professor those containing span 40 was found to encapsulate Department of Pharmacuetics, KMCH College of 48.21%. This showed that span 60 is the more suitable Pharmacy, Coimbatore -35, Tamilnadu (INDIA) for his surfactant along with cholesterol for enhancing valuable support. We would also like to thank our maximum entrapment for the drug Pregabalin. Further, colleagues, lab assistants for their support. the percent drug entrapment is increased by decreasing References
the sonication time. Therefore, the sonication time was 1. R Fisher, Van Emde Boas W, Blume W, Elger optimized to 15 minutes and further reduction in the C, Genton P, Lee P. Epileptic seizures and size by increasing sonication time was not attempted. The formulated niosomes were subjected to in vitro International League Against Epilepsy (ILAE) drug release using 0.1M in tubing. The amount of and the International Bureau for Epilepsy spectrophotometrically at 215nm. The percentage 2. Malhotra M. and Jain N.K. Niosomes as Drug amount of free drug released was 99.04% within 2.5 Carriers. Indian Drugs, (1994), 31 (3): 81-86. hours. FI showed 84.99 % of drug release within 19 3. Buckton G., Harwood, Interfacial phenomena hours. F II showed 93.48 % of drug release within 20 hours (Table 4). These results showed that niosomal Publishers, Switzerland (1995); 154-155. pregabalin has sustained release upto 20 hours whereas 4. Baillie AJ, Coombs G.H. and Dolan T.F. Non- free Pregabalin was released within 2.5 hours. This is ionic surfactant vesicles, niosomes, as delivery because the drug is released slowly for a prolonged system for the anti-leishmanial drug, sodium period of time in niosomal Pregabalin. Storage under stribogluconate. J Pharm Pharmacol (1986); refrigerated condition showed greater stability with 97.23% of drug content at the end of 3 months whereas 5. Yoshioka T, Stermberg B. and Florence A.T. storage under room temperature and at 400C ± 20C, RH 70 % ± 5% showed drug content of 93.92% and (niosomes) of sobitan monoesters (Span 20, 40, 84.83% at the end of three months (Table 3). 60, and 80) and a sorbitan triester (Span 85). Conclusion
Niosomes containing Pregabalin was formulated using 6. Chauhan S and Luorence MJ. The preparation two surfactants such as span 40 & span 60 and evaluated for various parameters. From the above surfactant vesicles. J Pharm Pharmacol (1989); studies, it is concluded that Pregabalin encapsulated in niosomes showed prolonged release & longer duration 7. Gayatri Devi S, Venkatesh P and Udupa N.
of action thereby achieving sustained release. Niosomal sumatriptan succinate for nasal administration. Int J Pharm Sci (2000); 62 (6), Table 1: Preparation of Niosomes
Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 4, Issue 7: July: 2013, 2770-2774
Research Article [Kumar et al., 4(7): July, 2013]
CODEN (USA): IJPLCP ISSN: 0976-7126
Table 2: Vesicle diameter of niosomes and % drug entrapment
Type of formulation
Size (nm)
% Drug Entrapment
Table 3: Stability Studies
Amount of drug retained (%) after 3 months
Temperature
Formulation I
Formulation II
Table 4: Invitro drug release studies of FI and FII
Time (hrs)
Percentage drug diffused (FI)
Percentage drug diffused (FI)
Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 4, Issue 7: July: 2013, 2770-2774
Research Article [Kumar et al., 4(7): July, 2013]
CODEN (USA): IJPLCP ISSN: 0976-7126
Fig. 1: SEM photograph of F-I
Fig. 2: SEM photograph for F-II
Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 4, Issue 7: July: 2013, 2770-2774

Source: http://ijplsjournal.com/issues%20PDF%20files/july-2013/2.pdf