INTRODUCTION:

Indian researchers are trying to engineer effective drug delivery system through nanoparticles. The use of nanotechnology enables researchers to encapsulate medicine in tiny particles which are the size of viruses. Nanoparticles can be designed to carry and deliver drugs to very precisely diseased cells. This way drugs can be delivered in small dosage as well as in sustained release, thereby minimising side effects. One such simple concept for achieving sustained release of drugs using the nanoparticle system is Solid lipid nanoparticles. Conventional drugs administered to patients get easily cleared from the body, which makes frequent administration of the drugs necessary. This makes patient compliance an important factor that determines efficiency of treatment.

Nanoparticles have been investigated as drug carriers as they can sustain the release of drug and increase blood circulation time of a drug. Thus it can reduce its side effects on healthy tissues and improve the treatment efficiency. Our system can be used to deliver a drug on demand for longer period of time, thereby improving the drug efficiency and reducing the frequency of drug administration. Additionally, one can load different types of drugs used in combinatorial therapy and control the sequence of their release in body using nano drug delivery system. Sustained release of drugs on demand is still a challenge in the field of drug delivery that motivated us to work towards designing a simple system that can help to achieve a sustained release of drug from nanoparticles.

The t_1/2 of a substance is the time takes for a substance to loss half of its pharmacologic, physiologic or radiologic action^[1]. The connection between the biologic and plasma half existence of a substance in view of the substance because of factor incorporating accumulation in tissue, dynamic metabolites and receptor cooperation^[2]. Ernest Rutherford's discovered the term t _1/2 period in 1907, was condense to half-life in the early 1950s^[3]. There are different types of half-life physical half-life, biological half-life and Radio-ecological half-life^[4]

Physical half-life is characterized as the time period taken to lessen the radioactive source to precisely one portion of its unique or introductory incentive because of rot of radioactive. The physical half-life is indicated as t_1/2. Biological Half-life is said to be the time tired required to decrease the medication sum in an organ or the body to precisely one portion of its unique or introductory incentive due exclusively to natural disposal. Radio-natural half-life is even less exact than the physical and biological half-life. Radio-biological half-life is characterized as the radioactive half-life for the creatures and plants living in the region. It shifts for the distinctive sorts of creatures and plants^[4].

Nanotechnology has globular structure and encases interior pits. Its size is under 10nm^[5]. This Pharmaceutical nanotechnology is isolated in two principal sorts of nano apparatuses viz. nano materials and nano gadgets. These materials can be sub grouped into nano crystalline and nano organized materials. Nano structure comprises of polymer and non-polymer. In polymer, it tends to be subdivided into nano particles, dendrimers, micelles, tranquilize conjugates. In non-polymer, metallic nano particles, Carbon nano tubes, quantum dab, silica nanoparticle^[6]. Carbon nanotubes are little macromolecules that are interesting for their size, shape, and have one of a kind physical property. Nano-tubes have some exceptional focal points over the other medication conveyance framework and symptomatic frameworks because of physical properties which are special in nature. Metallic nano molecule have help in tranquilize conveyance, particularly in treatment of malignancy and furthermore in biosensors. Among different metals, silver and gold nano particles are of prime significance for restorative utilize. Dendrimers are hyper spread, tree-like structures. It contains three unique areas: center moiety, expanding units, and firmly pressed are utilized for long circulatory, controlled conveyance of bioactive material, directed medication conveyance of bioactive particles to macrophages and liver focused on conveyance^[7].

Disintegration testing is a standout amongst the most generally utilized and a prerequisite for all pharmaceutical measurements shapes. It is utilized in all periods of advancement for the arrival of dynamic item and the dependability testing^[8]. It is one of the imperative test utilized for distinguish physical changes in a functioning pharmaceutical fixing (API) and in the planned item^[9]. In Research and Development, the identification of basic assembling factors and the similar examinations for In vitro– In vivo connection (IVIVC) has been utilized for in the course of recent years^[10]. The particular disintegration system is utilized for the assurance of dose frame qualities and the proposed route of administration. For solid dosage forms, there are several apparatus used according to the United States Pharmacopoeia (USP) there are seven types of apparatus and according to the Indian Pharmacopoeia (IP) there are two types of apparatus used whereas according to the British (BP) and European pharmacopoeia (EP) there are of three types of dissolution apparatus^[11,12]. The most commonly used apparatus are as follows; Basket type (Apparatus 1) the Paddle type (Apparatus 2). Other dissolution techniques and equipment include Reciprocating Cylinder type (Apparatus 3), Flow through-cell type (Apparatus 4), Paddle-over disk type (Apparatus 5), Cylinder (Apparatus 6) and reciprocating holders (Apparatus 7). The Floating capsules and tablets generally use USP 1 baskets Type. Orally disintegrating tablets, chewable tablets, CR, suspensions generally use USP 2 paddle type. For transdermal system the most commonly used apparatus are paddle over disc type and cylinder type^[12].

MATERIALS AND METHODS:

Solid Lipid Nanoparticle:

A solid lipid nanoparticle or SLN, diameter is about 10 to 1000 nanometers and is spherical in shape. Surfactant is used to stabilize the lipid core^[13]. The term lipid includes triglycerides (e.g. tristearin), diglycerides (e.g. glycerol bahenate), monoglycerides (e.g. glycerol monostearate), fatty acids (e.g. stearic acid), steroids (e.g. cholesterol), and waxes (e.g. cetylpalmitate). The combination of two or more emulsifiers might prevent particles agglomeration more efficiently in solid lipid nanoparticle^[14].

Table 1: Description of USP apparatus

USP Apparatus	Description	ROT. Speed	Dosage Form
1	Basket	50-120 rpm	Conventional tablets, chewable tablets, CR
2	Paddle	25-50rpm	Orally disintegrating tablets, chewable tablets, CR, suspensions
3	Reciprocating cylinder	6-35rpm	CR, chewable tablets
4	Flow through cell	Not applicable	ER, poorly soluble API, powder, granules, microparticles, implants
5	Paddle over disk	25-50rpm	Transdermal
6	Cylinder	Not applicable	Transdermal
7	Reciprocating holder	30rpm	CR (non-disintegrating oral and transdermal)

Preparation of Solid Lipid Nanoparticle:

Hot homogenization is similar to the homogenization of an emulsion; the temperature is carried out above the melting point of the lipid. By high-shear mixing device like silvers ion-type homogenizer the pre-emulsion of the drug loaded lipid melt and the aqueous emulsifier phase (same temperature) is obtained. As there is change in the quality of the pre-emulsion, the quality of the final product affects to a great extent and it is desirable to obtain droplets in the size range of a few micrometers. High pressure homogenization of the pre-emulsion is done above the melting point of lipid. Because of lower viscosity of the lipid phase at higher processing temperatures, the lower particle sizes are obtained^[15], although this might also accelerate the drug and carrier degradation. After several passes, typically 3-5 passes through the high-pressure homogenizer (HPH) produces better quality products^[16]. In most cases, 3-5 homogenization cycles at 500-1500 bar are sufficient. If a particle possess the high kinetic energy, the size of the particle increases due to increasing of the homogenization^[17,18].

Characterization of Nanoparticle:

Transmission Electron Microscopy Examination:

Using a negative staining-design, knowledge regarding the complex and size of the Mefenamic acid and Mosapride solid lipid detected by Transmission electron microscopy (TEM). On a 200-mesh copper grid, a droplet of SLN dispersion was spread and by using the suitable filter paper excessive droplets were removed^[19]. To the grid of copper a droplet of phosphortungstic acid solution 4% (w/v) was dropped or added. Under optimum temperature, they are air- dried after staining process and the samples were finalized of the TEM investigation^[20,21,22].

Particle Size & Zeta Potential Determination:

The electric charge reflected by zeta potential on the surface of the particle and physical stability of colloidal systems and the particle size was measured using Malvern Zetasizer (Malvern Instruments, UK)^[23-25].

In-vitro Dissolution:

Mosapride and Mefenamic acid nanoparticles were formulated and subjected to in-vitro release profile with an aid of simple diffusion cell apparatus. A glass tube (diameter of 2.5cm) with one end tied with artificial dialysis membrane serving as donor compartment and other end left as such. Marketed release formulation was to be compared with the nano formulations and therefore the release profile of the same was carried out using USP – type II dissolution apparatus (paddle type). 900ml of the dissolution medium (pH 7.4) was placed in to the dissolution. The temperature got to be maintained at 37 ± 0.5^oC with 50rpm^[26]. The dissolution apparatus was to be served with one mosapride tablet and one mefenamic acid tablet, and allowed to run for 10 hours. 10ml sample was withdrawn after every 1 hour intervals up to 10 hours. As it is to maintain the volume of dissolution medium, a fresh sample was replaced every time. Dilutions were made with the collected sample and analyzed at 286 nm using pH 7.4 as blank. The percentage of the drug release was calculated^[27,28].

RESULT AND DISCUSSION:

Transmission Electron Microscopy:

Knowledge regarding the complex and size of the Mefenamic acid and Mosapride solid lipid nanoparticle was detected by Transmission electron microscopy (TEM). Various characteristics such as particle shape and internal structure of the nanoparticulate carrier system can be efficiently observed by using TEM. Transmission electron microscopy was used to take photos, TEM images revealed the spherical shape of the particles of Mefenamic acid and Mosapride.

Figure 1: TEM of Mefenamic acid

Figure 2: TEM of Mosapride

Determination of Particle Size and Zeta Potential:

Figure 3: Particle size of Mefenamic acid

The particle size and surface charge of the particles, zeta potential were made for the Mefenamic acid and the Mosapride. The particle size of Mefenamic acid and the Mosapride were found to be about 180nm and 190nm respectively. Zeta potential measurements were performed for Mefenamic acid and Mosapride SLN. All the obtained zeta potential values were negative in charge because of the presence of glyceryl monostearate which is a fatty acid ester. Stable dispersion of particles is possible when the absolute value of zeta potential is above 25mV (both negative and positive) because of the repulsions produced by the surface electric charge of the particles in the dispersion. Lower zeta potential values may lead to inter particulate interaction resulting in flocculation and coagulation. As the obtained zeta potential values for Mefenamic acid and Mosapride SLN were over negative 25mV and 28mV. The SLNs were found to be physically stable.

In-vitro Dissolution Study:

A sustained drug release over a period of 8 hours has been noted with the nanoparticles of Mefanamic acid and Mosapride. The percentage drug release of Mefanamic acid (marketed formulation) was observed to be 36% at first hour and 98% at second hour.

Figure 6: Zeta potential of Mosapride

Table 2: Comparative Dissolution Study of Different Formulation

Sl. No	Time (Hr)	Drug release of mefanamic acid (%)	Drug release of mosapride (%)	Drug release of sln mefanamic acid (%)	Drug release of sln mosapride (%)
1	0	0.00	0.00	0.00	0.00
2	1	36.672	10.28	10.46	8.04
3	2	98.753	23.56	19.25	17.58
4	3	-	38.75	28.43	26.09
5	4	-	51.25	40.40	38.21
6	5	-	64.35	52.25	51.02
7	6	-	77.23	67.53	65.68
8	7	-	89.12	79.23	77.06
9	8	-	99.52	91.42	89.13

With respect to the nanoparticle (SLN) of the same, the percentage release was found to be 10.46% at first hour, 52% at fifth hour and during eight hour the percentage release was found to be 91%.

The percentage drug release of Mosapride (marketed formulation) was found to be 10.28% at first hour, 64.35% at fifth hour and 99.52% at eight hour.With respect to the nanoparticle (SLN) of the same, the percentage release was found to be 8.04% at first hour, 58.02% at fifth hour and during eight hour the percentage release was found to be 89.13%. We noted a significant difference in the percentage drug release of Mefanamic acid with its SLN which was not observed in the latter drug.

Figure 7: In-vitro Drug Release

Series 1:- %of Drug Release of Mefanamic Acid

Series 2:- %Drug Release of Mosapride

Series 3:- %of Drug Release of SLN Mefanamic Acid

Series 4:- %Drug Release of SLN Mosapride

CONCLUSION:

In conclusion, Mefenamic acid and Mosapride was successfully loaded into Solid lipid nanoparticles. The obtained nanoparticles were within the characterization limit as expected. In vitro release studies showed significant sustained release from the nanoparticles. These works contribute to improve Mefenamic acid and Mosapride clinical use, and further develop drug carriers for achieving sustained and controlled release for the drugs in demand.

AUTHOR CONTRIBUTION:

Keerthi G S Nair- Carried the research work, data analysis and written the manuscript Ramaiyan Velmurugan-Reviewed the manuscript Sathesh Kumar S Approved the manuscript

ACKNOWLEDGEMENT:

The authors are thankful to the School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies, and its management for providing research facilities and encouragement.

CONFLICT OF INTEREST:

The authors acknowledge no conflicts of interest in this study.

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Received on 07.11.2019 Modified on 15.01.2020

Research J. Pharm. and Tech. 2020; 13(11):5391-5395.

DOI: 10.5958/0974-360X.2020.00943.9