Formulation and Evaluation of Nimodipine Tablet by Liquisolid Technique

Copyright © 2019 by author(s) and International Journal of Trend in Scientific Research and Development Journal. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) (http://creativecommons.org/licenses/ by/4.0) ABSTRACT Liquisolid technique is novel concept of the drug delivery via the oral route. This technique is applied to poorly water soluble , water insoluble or lipophilic drugs. According to the new formulation method of liquisolid compact, liquid medication such as solution or suspensions of water insoluble drug in suitable nonvolatile solvent can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. The present work endeavour is directed towards the development of liquisolid compact for production of immediate release tablet of water insoluble Nimodipine. Liquisolid compacts were prepared by using polyethylene glycol 300 as the liquid vehicle or non volatile solvent. Crospovidone was used as a superdisintegrating agent and PVP K30 as a binder. Microcrystalline cellulose was used as a absorbing carrier and silicone dioxide as adsorbing coating material. The prepared liquisolid system were evaluated for their micromeretic properties and possible drug-excipients interaction . The FTIR spectra study ruled out any interaction between the drug and excipients in preparation of Nimodipine liquisolid compact. The in-vitro dissolution study confirmed enhance drug release from liquisolid compacts by using USP type I basket in 0.5 % SLS in water. The selected optimal formula released 93.86 % of its content in 30 min which is showing immediate release. The results showed that use of superdisintegrants had remarkable impact on the release rate of Nimodipine from Liquisolid compact, enhancing the release rate of the drug from liquisolid compact.


INTRODUCTION
Oral route is most common and popular route of administration of drug because of its systemic effect, patient compliance, less expensive to manufacture, safe and effective etc. Tablet form is the most widely used dosage form because of self-administration and ease in manufacturing. Tablet provides high precision dosing. In most of the cases immediate on set of action is required as compare to conventional therapy. To achieve the rapid onset of action and eliminate the drawbacks of conventional therapy immediate release dosage form is now a days popular and used as a alternative oral dosage form. Immediate release tablets are very quickly absorbed after administration. Basic approach used in development is the use of superdisintegrants which provide rapid disintegration of tablet after administration. 1 Nimodipine belongs to the class of pharmacological agents known as a calcium channel blockers. Nimodipine is used as a antihypertensive and in subarachnoid hemorrhage and Arrhythmias. It increases blood flow to injured brain tissues. The bioavailability is 13% by oral route were 95% of protein binding. It get metabolise in liver and biological half life having 8-9 hours and drug is excreted from Faces and urine 2 .
Many techniques are being employed for the solubility enhancement of poorly soluble drugs to resolve the bioavailability issue due to inadequate dissolution rate. Various approaches make use of hydrophilic polymers as solubility enhancers acting through a variety of mechanisms such as amorphization, co-solvency, micelle formation or inclusion complexes 3,4,5 . These techniques impart many advantageous effects in the formulation development. But usually these approaches show lack of stability and decreasing success rate over a period of storage. One of the remarkable demerits of solid dispersions, glass solutions, eutectic mixtures and inclusion complexes is formation of sticky and hygroscopic mass resulting in the poor flow characteristics. Due to this set-back, industrial feasibility of the final dosage form becomes very difficult 6,7,8 .
The liquisolid technology emerged as a new drug delivery system distinguished by its characteristics and ability to deliver variety of drugs 9,10 . Liquisolid drug delivery system has gained attention of pharmaceutical researchers due to its contribution in the solubility enhancement as well as dissolution retarding approaches depending on the need and design of the formulation 11,12,13 . Three major components in the formulation of liquisolid compacts are liquid medication, carrier and coat material 14 .

Fig.1: Concept of Liquisolid formulation
The aim of the present work is to increase the solubility and in-vitro dissolution of water insoluble drug Nimodipine by formulating it into liquisolid tablets.

Solubility studies
For the selection of best non-volatile solvents, solubility studies were performed. In this procedure, pure drug was dissolved in non-volatile solvents (propylene glycol and polyethylene glycol, Tween 80) . Excess amount of pure drug was added to the above solvents. Obtained saturation solutions were shaken on sonicator for 1 hours at 25 0 C under constant vibration. After 1 hours saturated solution were filtered and analyzed by UV spectrophotometer.
Calculation of loading factor (Lf) and "q" value Loading factors were calculated for different carriers, using various solvents. By using Lf = W/Q formula (W: Amount of liquid medication and Q: Amount of carrier material), the drug loading factors were obtained and used for calculating the amount of carrier and coating materials in each formulation. The results showed that if the viscosity of the solvent is higher, lower amounts of carrier and coating materials are needed to produce flowable powder. Based on R value used, the corresponding q (amount of coating material) can be calculated for all formulations using the equation R =Q/q.  5. After that it get dried in hot air oven at 60ᵒC for 1 hour. 6. Then the blend is pass through sieve no 20. 7. To this blend add aerosil as a coating agent and mix with Magnesium stearate to enhance the flow. 8. After complete mixing compression of the tablet with punch pressure having size 7.5mm or 10mm.

POST COMPRESSION ASSESMENT OF SUBLINGUAL TABLET
The tablets of all the batches were evaluated for weight variation, drug content, hardness, thickness, disintegration time, wetting time, water absorption ratio, moisture content and in-vitro dissolution study.
Weight Variation: 10 tablets were selected randomly from each batch and weighed individually to check for weight variation. The following percentage deviation in weight variation is allowed as per USP. Thickness and Diameter: The thickness and diameter of 4 tablets from each formulation were recorded during the process of compression using Vernier caliper.
Hardness: Pharmatorn hardness tester was used for the determination of hardness of tablets. Tablet was placed in between the plungers and the force of the fracture was recorded.
Friability: 6.5 gm. of tablets were accurately weighed and placed in the friabilator (Electrolab, EF-2 Friabilator) and operated for 100 revolutions. The tablets were de-dusted and reweighed. Percentage friability was calculated using the following formula Where, W0 is the weight of the tablets before the test and W is the weight of the tablet after the test. The tablets that loose less than 1% weight were considered to be satisfactory.
Disintegration Time: Six tablets were taken and introduced in each tube of disintegration apparatus, and the tablet rack of the disintegration apparatus was positioned into a one liter beaker containing 900 ml of distilled water and the time of disintegration was recorded. To discriminate between the formulations disintegration was done at room temperature and disk was not used for the study. Absorbance of this solution was measured at 240 nm.

Identification tests for Nimodipine
A. Melting point: The melting point of the Nimodipine was found to be 125 °C which complies with melting point reported one.

B. UV Scanning:
The λmax of Nimodipine was found to be 240 nm. This complies with specified λmax.

In-vitro Drug Release from Nimodipine Liquisolid Compact.
In-Vitro dissolution studies were carried out using USP apparatus type I at 50 rpm. Dissolution medium consist of 0.5 % SLS in water maintained at 37ᵒC . Drug release at different time intervals was measured by UV-Visible Spectrophotometer at 240 nm.
In-vitro drug release drug release profile of all batches was compared with conventional formulation for drug release. Dissolution study was performed using USP Dissolution apparatus I (basket type), using 900 ml dissolution medium 0.5% SLS in water with a rotation speed of 50 rpm.
The release of drug from these formulations provide evidence that PEG 300 play an vital role in immediate release of drug from liquisolid compact.
Thus, it can be concluded that formulation of Nimodipine tablet by Liquisolid Technique with appropriate ratio showed better disintegration time and percent drug release than other formulation. As all parameters were found satisfactory for small scale batch, it need to check commercial feasibility at larger scale. Hence it can be very well recommended for launching the proposed formulation in market with some desirable changes if required.