Irbesartan Formulation and Evaluation of Loaded Solid Lipid Nanoparticles by Microemulsion Techinque

 

Ashok P.1*, Meyyanathan S. N.1, Jawahar N.2, R. Vadivelan3

1Department of Pharmaceutical Analysis, JSS College of Pharmacy,

JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India.

2Department of Pharmaceutics, JSS College of Pharmacy,

JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India.

3Department of Pharmacology, JSS College of Pharmacy,

JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India.

*Corresponding Author E-mail: jeeashok77@gmail.com

 

ABSTRACT:

In this study for solid lipid nanoparticles prepared technique is by microemulsion. Initially, o/w microemulsion was synthesized. The glyceryl tripalmitate (GTP) is oil phase. Lipophilic surfactant as Soy lecithin and and in continuous phase, hydrophilic surfactant (Pluronic F-68) solution was used. Drug was added under stirring after soy lecithin was melted at 70oC, Pluronic F-68 as aqueous surfactant solution about 10mL added by maintaining same temperature to the liquefies lipid with continuous automatic stirring for 15 minutes. When the temperature was close to the melting point of the lipid in the formulation a clear microemulsion was obtained under stirring. To induce positive charge, stearyl amine is used and loaded to melted lipid. Continuous stirring of solid lipid nano particles were attained by dissipating the tepid o/w microemulsion drop wise into freezing water in a glass beaker. After complete addition of microemulsion, SLN dispersion was further stirred. Ultrasonication was carried out for 15 minutes for SLN formulation, then centrifuged and freeze dried. The optimized batch was also evaluated for various parameters such as particle size, zeta potential and surface morphology. Also, optimized formulation was compared for in vitro drug release with drug solution.

 

KEYWORDS: Solid lipid nanoparticles, Irbesartan (IRB), microemulsion.

 

 

INTRODUCTION:

Irbesartan (IRB) used mainly for hypertensiontreatment. It belongs to class II drug according to Biopharmaceutical Classification System. Irbesartan has a half life of 11-15 hours and the usual initial and maintenance dose is 150mg once daily. Irbesertan do not produce adverse effect of dry cough.

 

Irbesartan is a nonpeptide tetrazole derivative and an angiotensin II antagonist that relatively blocks the binding of angiotensin II to the AT1 receptor. It is biotransformed via Glucoronide conjugation and oxidation and excreted by both biliary and renal routes. In the market, we can procure Irbesartan as white and off-white biconvex oval tablets in different strengths (75, 150 and 300mg).[1]

 

In 1991, Solid Lipid Nanoparticles were referred to as anpreferred carrier system to tradition colloidal carriers such as - Emulsions, liposome’s and polymeric micro and nanoparticles. SLN are aqueous colloidal dispersions which comprises of solid biodegrada blelipids. SLN are sub-micron colloidal carriers ranging from 50 to 1000 nm. An SLN is generally globular in shape and coheres of a solid lipid core which is controlled by surfactants (emulsifiers). SLN deliverpeculiar properties such as minute size, huge Surface area, elevated drug loading, and the junctionof phases at the interface and are appealing for their potential to enhance performance of pharmaceuticals[2]. One of the emerging fields of nanotechnology is solid lipid nano particles with manycompelling applications in novel drug deliveryand clinicalresearch. The newly synthesizednanoparticles as drug-carrier system is a very attractive possibility to achieve controlled drug delivery. A main advantage of SLN over polymeric nanoparticles is the truth that the lipid matrix is synthesized from physiologicallipids, whichreducetherisk ofacute andchronictoxicity.

 

In process for overcoming issues involving solubility and dissolution rate of low soluble drug, many technologies have been employed including complexation, solid dispersion techniques, microemulsion and nature emulsifying drug delivery systems. The use of solid lipid nanoparticles (SLNs) suggests a new perspective in the formulation of poorly soluble drugs. SLNs have gained increased attention in the pharmaceutical and food industries. SLNs combine the advantages of polymeric nanoparticles, fat emulsion and liposome. SLNs are widely used to improve bioavailability and to achieve sustained release.

 

MATERIALS AND METHODS:

Materials:

Irbesartan was procured from reputed pharmaceutical company. Stearic acid (lipid), PVA (stabilizer), and tween 80 (surfactant) were also obtained. All other chemicals and reagents used in this study were of analytical grade.

 

Experimental design of solid lipid nanoparticles loaded with Irbesartan:

Formulations were prepared by applying full factorial designs. Stearic acid (lipid) and PVA were considered as independent variable whereas entrapment efficiency, drug loading and in-vitro release considered as a dependant responses. Amount of drug (50mg) and tween 80 concentrations (0.125%) were kept constant throughout formulation process. The factorial designs for each formulation are as follows:

 

Method of preparation:

Preparation of Solid Lipid Nanoparticles:

The synthesisof nano suspension was achieved by solvent diffusion method. Drug was accurately weigh, the same were dissolved in 2ml of Organic phase (Acetone) required amount of surfactant was dissolved in 20ml of water by using continuous stirrer. The loading of drug solution was performed with micro level addition to the above solution and was mixing with 3000rpm for about 30minutes and later sonicated at 80 amplitude for 15minutes. Cryo-protectant Mannitol was added before freeze drying. The prepared suspension was exposed to lyophilisation and the dried product was composed and performed illustrated.

 

Optimization of solid lipid nanoparticles:

The responses such as Entrapment efficiency (EE), Drug loading (DL) and in-vitro release for prepared formulation were measured to optimize the formulation.

 

Drug Entrapment Efficiency:[3]

Separation of free drug: The separation was done by centrifugation at 10000 RPM for 15 minutes of SLNs. Then, the nanoparticles pellets and supernatant were separated out.

 

Entrapment efficiency in the nanoparticles were determined by the following formula, (Snjezana stolnik et al 1999)

 

                         (Mass of the drug in nanoparticles)

Entrapment = -------------------------------------------- × 100

efficiency    (Mass of the drug used in the formulation)

 

Drug loading capacity:[4]

% Drug loading was calculated using following equation.

 

                             Drug entrapement in SLNs

% Drug = -------------------------------------------------× 100

Loading            Total Weight of drug + polymer

 

In vitro drug release:[5]

The dialysis bag distributionmethod was used to study the in-vitro drug release of irbesartan nanoparticles. 5ml of SLNs counterpart to 1mg were kept in dialysis bags. The dialysis bags were placed in 50mL of disso medium and for uniformity done withcaptivating stirring at 37ºC. Fractions of the dissolution medium were kept aside and at each time interval and restored with same amount of dissolution medium to maintain a constant volume. Samples taken at each time interval from phosphate buffer pH 7.4 were assessed for drug content by UV at wave length maxima of the respective drug against solvent blank.

 

To determine theapproach and mechanism of drug release, the In-vitro data was statistically analysed and construed at interface tocreatewith Istorder and Higuchi’s respectively.

 

Characterization of optimized SLN:

Particle size and Zeta potential:

The optimized batch was evaluated for particle size and zeta potential to determine whether the charged particle is encapsulated within the centre or adsorbed on to the surface of SLNs.

 

It was found that batch PNF5 had -12.9 Mv in PLGA-Nanoparticles. Batch prepared without Stearyl amine had zeta potential of -1.97mV, which might be reflux to negative ion charge distributed at surface of SLNs due to Gleceryl tripalmitate, while batch synthesized with Stearyl amine had zeta potential of 37.2millivolt. Whereas batch NSF6 had 29.37mV in nanosuspension confirms that these surface charges favours the static stability of the particles.

 

PI values of all the synthesis obtained designate that particle size allocationis being considered as unimodel. The customised batch SLNFI-5 having the particle size of 256 nm had a PI of 0.712 respectively.. The PI value confirms the particles had physical stability.

 

Scanning Electron Microscopy (SEM):

SEM confirms obtained nanoparticles were spherical in shape. The nanoparticles size observed by SEM correlated well with the particle size measured by Malvern instrument.

Statistical analysis:

Statistical analysis was performed using the one-way ANOVA method. Results were interoperated and expressed as mean ± SD. The differences were considered vital at the level of p < 0.05.

 

RESULTS AND DISCUSSION:

The formulated nanodrug delivery systems achieved desirable physico-chemical and biopharmaceutical properties of poorly soluble drugs (irbesartan as BCS Class II). Among the formulations, solid lipid nanoparticles revealed a significant increase (4 fold) in oral bioavailability compared to raw drug suspension.

 

FT-IR studies:

FT-IR studies indicated that the peaks present in FTIR spectra of drug was also present in physical mixture. Therefore there was no interaction found between drug, lipid and polymer and can be confirmed that they are compatible. (Figure 1)

 

 

Figure 1: FT-IR Spectrum in range of 4000 to 400 cm-1: Pure drug (A); and mixture of drug, SLN 3

 

CONCLUSION:

Optimization of an SLN formulation is a complex process. From results, it can be concluded that poorly water soluble drug Irbesartan (IRB) was successfully inbuilt into solid lipid nanoparticles by a micro-emulsion method. Dose of the drug loaded SLN should to be measured in accordance with increased bioavailability, to decrease its dosage related adverse effects. SLNs provided controlled release of the drugs, and these schemes are the preferred drug carriers for lipophilic drugs to triumph over the bioavailability problems in chronic diseases by means of improved bioavailability and reduced toxicity.Thus, these delivery systems may prefer to improve the oral bioavailability of poorly soluble irbesartan drugs. The in vitro release study showed that it exhibiting controlled release for 24 hrs. It can be confirmed that the liberate velocity of the SLNs is always rapid compared with the diffusion rate of the IRB solution. Thus, SLNs may constructdrasticenhancement in the bioavailability of irbesartan evaluate with raw drug solution.

 

REFERENCES:

1.      Husain A, Mitra SA, Bhasin PS. A Review of Pharmacological and Pharmaceutical profile of Irbesartan. Pharmacophore2011; 2(6):276-86.

2.      Ramteke KH, Joshi SA, Dhole SN. Solid lipid nanoparticles: A review. IOSR Journal of pharmacy2012; 2(6):34-44.

3.      Rabea P, Ahmad FJ, Samim M, Ahmad S. Solid lipid nanoparticles of anti cancer drug Andrographolide: Formulation, in vitro and in vivo studies. Drug Dev Ind Pharm 2014; 40(9):1206-12.

4.      Luo Y, Chen D, Ren L, Zhao X, Qin J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release2006; 114:53-59.

5.      Hu LD, Tang X, Cui FD. Solid lipid nanoparticles to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol2004; 56:1527-1535.

 

 

 

Received on 15.05.2020            Revised on 13.06.2020             

Accepted on 11.07.2020      ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2020; 10(4):228-230.

DOI: 10.5958/2231-5713.2020.00038.0