PREPARATION AND CHARACTERIZATION OF NIOSOMES CONTAINING ACECLOFENAC

About Author:
Patel Sanjay P
Sanjeevan College Of Pharmacy,
Behind Shyam Sarovar Township,
Jaipur-Agra Highway,Dausa-303303,Rajasthan
sanonly4frdz@gmail.com,sanjay_411987@yahoo.com

1.Abstract
Aceclofenac is a drug with narrow therapeutic index and short biological half-life, so can achieve steady state concentration rapidly. This study was aimed at developing and optimizing niosomal formulation of aceclofenac in order to improve its bioavailability as compare to liposomes.This niosome is prepared by modified ether injection technique. In this span 60 & span 20 is used as non ionic surfactants. Different 6 formulation are prepared, In this NFS-1 to 3 formulation are prepared using the span 60 & NFS-4 to 6 are prepared using span 20 along with different proportion of cholesterols. Because of the presence of nonionic surfactant with the lipid, there is better targeting of drugs to tumor, liver and brain. In evaluation study, the effect of the varying composition of non ionic surfactant and cholesterol on the properties such as drug entrapment efficiency, drug content, particle size & shape and drug release were studied. Moreover, the release of the drug was also modified and extended over a period of 72 h in all formulations. NSF-3 emerged as the most satisfactory formulation. Further, release of the drug from the most satisfactory formulation NSF-6 was evaluated through dialysis membrane to get the idea of drug release. The mechanism of dug release was governed by K- Peppas model. In all the niosomes prepared with spans, as the concentration of surfactant increased drug entrapment efficiency increased. Among the spans, span 60 having high phase transition temperature (gel to liquid transformation) and having critical packing parameter (CPP) ranging from 0.5 to 1 entrap drug molecule without any cholesterol. The only drawback of span 60 vesicles was rapid leakage of drug from the vesicle because of high phase transition temperature. In all the cases the best fit model was found to be Peppas with ‘n’ value between 0.65 to 0.73 suggesting the non fickian (anomalous) release mechanism for the drug i.e., erosion followed by diffusion controlled. Formulation NSF-6 showed high entrapment efficiency (96.07%±0.35), particle size (4.22±0.47μm) and drug release (87.21%) over 72 h. Hence it was considered to be good niosomal formulation with greater bioavailability.

Reference Id: PHARMATUTOR-ART-1333

2. Introduction
Niosomes or nonionic surfactant vesicles are microscopic lamellar structures formed on admixture of nonionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media [1]. In niosomes, the vesicles forming amphiphile is a nonionic surfactant such as span 60 which is usually stabilized by addition of cholesterol and small amount of anionic surfactant such as dicetyl phosphate[2]. Niosomes can entrap both hydrophilic and lipophilic drugs, either in aqueous layer or in vesicular membrane made of lipid materials. It is reported to attain better stability than liposomes. It can prolong the circulation of the entrapped drugs. Because of the presence of nonionic surfactant with the lipid, there is better targeting of drugs to tumour, liver and brain. It may prove very useful for targeting the drug for treating cancers, parasitic, viral and other microbial disease more effectively [3].
Aceclofenac belongs to non steroidal anti- inflammatory drugs (NSAIDs)[4-5]. It works by blocking the action of cyclooxygenase. Cyclooxygenase is involved in the production of various chemicals in the body, some of which are known as prostaglandins. Prostaglandins are produced in response to injury or certain diseases and would otherwise go on to cause pain, swelling and inflammation. Aceclofenac is used to relieve pain and inflammation in arthritic conditions. All the drugs in this group reduce inflammation caused by the body's own immune system and are effective pain killers. But it has several drawbacks such as narrow therapeutic index, short biological half-life. These factors necessitated niosomal formulation for aceclofenac. As this dosage form would reduce the dosing frequency, hence better patient compliance. The present study was aimed with the formulation of niosomes of aceclofenac followed by the evaluating parameters such as drug content, entrapment efficiency, particle size, shape, size distribution and in vitro drug release

3. Materials and methods
Aceclofenac was obtained from Rantus Pharmaceuticals Hyderabad, India; Spans were obtained from Rolex chemical industries, Mumbai. Diethyl ether Methanol, potassium dihydrogen phosphate, sodium hydroxide was obtained from S.D.Fine chemicals. All ingredients used were of analytical grade. Evaluation of raw materials Identification and standardization of drug and other excipients were carried out as per the official procedures mentioned in respective monographs. Preparation of Niosomes Niosomes containing aceclofenac were prepared by modified ether injection technique using nonionic surfactant (span 60, span 20) and cholesterol at different concentrations. Cholesterol and surfactant were dissolved in 6ml diethyl ether mixed with 2ml methanol containing weighed quantity of aceclofenac. The resulting solution was slowly injected using microsyringe at a rate of 1ml/min into 15 ml of hydrating solution phosphate buffer (pH 7.4).The solution was stirred continuously on magnetic stirrer and temperature was maintained at 60-65ºC. As the lipid solution was injected slowly into aqueous phase, the differences in temperature between phases cause rapid vaporization of ether, resulting in spontaneous vesiculation and formation of niosomes. Different batches of niosomes were prepared in order to select an optimized formula as per general method described above and proportion of surfactant and cholesterol for the preparations of niosomes is given in Table 1 and optimized niosomal formula are given in Table 2.

Table 1: composition of surfactant and cholesterol for preparation of niosomes.

Table 2: Optimized formula for the noisome preparation

Drug Entrapment efficiency of niosomes
Entrapment efficiency of niosomes was determined by exhaustive dialysis method. The measured quantity of niosomal suspension was taken into a dialysis tube to which osmosis cellulose membrane was securely attached on one side. The dialysis tube was suspended in 100ml phosphate buffer (pH 7.4), which was stirred on a magnetic stirrer. The unentrapped drug was separated from the niosomal suspension into the medium through osmosis cellulose membrane. At every hour entire medium (100ml) was replaced with fresh medium (for about 9-12h) till the absorbance reached a constant reading indicating no drug is available in unentrapped form. The niosomal suspension in the dialysis tube was further lysed with propane-1-ol and estimated the entrapped drug by UV spectrophotometric method at 274nm. The entrapment efficiency was calculated using following equation. Amount of entrapped drug Entrapment efficiency = X 100 Total amount of drug
Drug content
Niosomes preparation equivalent to 40mg of aceclofenac was taken into a standard vol flask. Then they were lysed with100ml of propane-1-ol by shaking. Then 1ml of this was subsequently diluted with phosphate buffer (pH 7.4). The absorbance was measured at 274nm and calculated drug content from the calibration curve.

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Particle size and shape analysis
Particle size analysis was carried out using an optical microscope with a calibrated eyepiece micrometer. About 200 niosomes were measured individually, average was taken and their size distribution range and mean diameter were calculated. Further microphotographs of optimized niosomes were taken by using 9 megapixel Sony DSC-W110 digital camera. The histogram for particle size distribution and particle size are shown in Figure 1a, 1b and the microphotographs are shown in Fig. 2a, 2b.