Preparation and Optimization of Fexofenadine HCl Solid lipid Nanoparticles

Ashwini Gunjote*, Heramb Shahane, Rani Ghosalkar, Kedar Bavaskar, Ashish Jain

Department of Pharmaceutics, Shri D.D Vispute College of Pharmacy and Research Center, Panvel.

*Corresponding Author E-mail: heramb.shahane19@gmail.com

ABSTRACT:

Solid lipid nanoparticles (SLNs) are introduced as an efficient carrier method for correcting dynamic medicine and water-soluble medication. Fexofenadine HCl is a long-acting selective histamine (H1) receptor antagonist with anti-inflammatory properties of the second generation. Allergic rhinitis, angioedema, and chronic urticaria are treated with fexofenadine HCl. Solid lipid nanoparticles were prepared by hot homogenization method using a solid lipid of and different polymers. A solid lipid nanoparticle created by drug and polymer poloxamer 188 in ratio showed highest entrapment efficiency as well as drug release of the medication from the solid lipid nanoparticle formulation. The prepared nanoparticles were used to formulate the nanogel using Carbopol 934. The nano-drug delivery system developed by the hot homogenization method has demonstrated their suitability for a topical route for the treatment of skin allergy. Thus, the studies revealed that the developed system has a great appeal for the convenient treatment of dermatological allergy that may overcome in improving the limitations of the existing drug delivery system. Fexofenadine HCl is a white colored powder. It is practically insoluble in water and soluble in methanol. The melting point was found to be 194.1-195.2. The FTIR spectra of Fexofenadine HCl and the mixture of drug and excipients used in the formulation of nanoparticles reveal that there was no significant interaction between the drug and polymer and other excipients used in the formulation. The optimized batches (F2) showed highest entrapment efficiency. It was observed that as there is increase in concentration of surfactant increases the entrapment efficiency. The optimized solid lipid nanoparticle formulation showed maximum drug release within 6 hr. This showed that the increase in the concentration of surfactant there was increase in drug release from the SLN.

KEYWORDS: Solid lipid nanoparticles, Fexofenadine HCl, gel, Tropical route, Entrapment efficiency.

INTRODUCTION:

In 1991 Solid lipid nanoparticles was introduced which represent an alternative carrier system to traditional colloidal carriers such as emulsions, liposomes and polymeric micro and nanoparticles. Solid lipid nanoparticles [SLN] consists of spherical solid lipid particles in the nanometer range, which are dispersed in water or in aqueous surfactant solution.¹

Synthetic or semi-synthetic polymers are the building blocks of nanoparticles, which are colloidal structures that have undergone sub ionization. The size of nanoparticles ranges from 10 to 1000nm. Solid lipid nanoparticles have a solid lipid core by a surfactant that is stabilised at the interfacial area. When making SLN, solid lipids are used in place of liquid lipids to improve physical stability and address the drawbacks of the liquid state^2,3. Nano-sized carriers, polymeric nanoparticles with easily tunable chemical and physical properties, can effectively protect unstable drugs from degradation/ denaturation, reduce the side effects of toxic drugs by producing controlled release, and improve drug penetration across the skin barrier by increasing the concentration barrier. In the last decade, nanosized drug carriers have gotten a lot of attention as potential ingredients in topical therapeutic formulations. By various advanced techniques SLNs are prepared. The site specific and sustained release effect of drug can better be gained by using SLNs.⁴ SLN combines advantages and avoid disadvantages of other conventional systems.⁵ The oral bioavailability of poorly water-soluble drugs and drugs prone for first-pass metabolism often exhibit low bioavailability as their absorption could be kinetically-limited by low rates of dissolution and capacity-limited by less solubility, when these were administered in traditional solid formulations.⁶

Fexofenadine HCl is the second generation, long lasting selective histamine (H1) receptor antagonist with anti-inflammatory property. Allergic rhinitis, angioedema, and chronic urticaria are treated with fexofenadine HCl⁷. When compared to other antihistamines, the likelihood of cardiotoxic effects associated with fexofenadine is considered to be extremely low. Fexofenadine may provide a safer alternative in the treatment of asthma and atopic dermatitis since it is fast absorbed and has a lengthy duration of action, making it appropriate for once-daily administration. Its half-life is approximately 14 hours, making it suitable for once-daily administration.^8,9 The current study attempted to manufacture and describe Fexofenadine HCl nanoparticles, which were then followed by drug-loaded Nano gel. An alternative carrier system to emulsions, liposomes, and polymeric nanoparticles Solid Lipid Nanoparticles (SLN) was developed over the past decade.¹⁰

Application of SLNs:

1. Cosmetics.

2. In Topical Drug Delivery System.

3. Release kinetics of drug can be controlled.

4. Targeted brain delivery of drug is made possible.

5. Targeting of anticancer drugs is made possible.

6. Enhanced biocompatibility of formulation.¹¹

MATERIALS AND METHODS:

Fexofenadine HCl is obtained as a gift sample from Cipla Limited Patalganga, Poloxamer 188, Poloxamer 407 and Carbopol (Glenmark Pharmaceuticals Limited), and all other ingredients used were of analytical grade.

Preparation of Fexofenadine HCl loaded solid lipid nanoparticles:

Hot homogenization method which includes the melting of lipids and dissolution of drug this method was used to formulate Fexofenadine HCl loaded solid lipid nanoparticles. Mix the preheated dispersion medium and drug lipid melt, premix the solution with stirrer to create a coarse pre-emulsion, and then perform high pressure homogenization at a temperature higher than the lipid melting point. The solid lipid nanoparticles are created by solidifying the nano-emulsion by cooling it to room temperature.¹²

Table 1: Composition of Fexofenadine loaded solid lipid nanoparticles containing different lipids and surfactants

Formulation	Solid lipid	% W/V	Surfactant	% W/V	Entrapment efficiency
F1	GMS	8	Poloxamer188	1	88.84%
F2	GMS	8	Poloxamer188	2	90.30%
F3	GMS	8	Poloxamer407	1	86.66%
F4	GMS	8	Poloxamer407	2	87.59%
F5	GMO	8	Poloxamer188	1	87.89%
F6	GMO	8	Poloxamer188	2	93.62%
F7	GMO	8	Poloxamer407	1	81.08%
F8	GMO	8	Poloxamer407	2	84.68%

Preparation of Gel Base:

Gel bases were created with various amounts of gelling agent, including 0.5, 0.75, and 1%. A specific amount of distilled water was filled in a 100ml beaker. propylene glycoland Methylparaben were accurately weighed and added to distilled water, which was then agitated at 50 rpm until entirely dissolved. in the aforesaid solution A predetermined amount of gelling agent was progressively dispersed then stirred for 60 minutes before being set aside for at least two hours.¹³

Preparation of Gel containing Fexofenadine HCl Nanoparticles:

In beaker the specified quantity of gel base was transferred. Second beaker containing the specific amount of propylene glycol. In the second beaker the drug loaded nanoparticles were transferred and mix well. To the beaker containing gel base transfer the drug-loaded nanoparticles solution and mix for 20 minutes. until the gel reaches the desired consistency add Triethanolamine to the aforementioned solution until the gel reaches the desired consistency add Triethanolamine to the aforementioned solution.¹³

Table 2: Formulation table of gel base containing Fexofenadine HCl nanoparticles

Sr.No.	Ingredients	Formulation
		I	II	III
1	Carbopol 934 (gm)	0.5	1	1.5
2	Methyl paraben (gm)	0.02	0.02	0.02
3	Propyl paraben (gm)	0.2	0.2	0.2
4	Drug-loaded nanoparticles (gm)	40	40	40
5	Propylene glycol (ml)	5	5	5
6	Triethanolamine (ml)	QS	QS	QS
7	Distilled water (ml)	100	100	100

EVALUATION OF SOLID LIPID:

Nanoparticles:

Entrapment Efficiency:

The entrapment efficiency of solid lipid nanoparticles was measured by the centrifugation method. solid lipid nanoparticles are dispersed (containing an equal to100 mg of drug. A solid lipid nanoparticle dispersion was centrifuged for an hour at 2000rpm in a chilled centrifuge to obtain the supernatant liquid. The recovered liquid was filtered to ascertain the concentration of free drug after an appropriate methanol dilution. to measure absorbance at 220nm a UV spectrophotometer was employed.^14,15

The percentage of the drug encapsulated within and adsorbed on to the SLN is the encapsulation efficiency (EE).¹⁶

The following formula was used to calculate the entrapment efficiency of solid lipid nanoparticles:

                                           W initial drug – W free drug

% Entrapment Efficiency = –––––––––––––––––– ×100

W initial drug

Particle size and zeta potentials:

A zeta potential analyzer or a zeta metre can be used to measure zeta potential. Prior to measuring, solid lipid nanoparticles dispersions are diluted 50-fold with the original dispersion preparation medium for size identification and zeta potential measurement. A higher zeta potential value may lead to particle disaggregation in the absence of any complicating components, such as steric stabilisers or hydrophilic surface appendages. Colloidal dispersion storage stability can be predict using zeta potential measurements.^17,18 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 with Malvern Zetasizer.^19,5

Scanning electron microscopy/ Particle size analysis:

By scanning electron microscopy (SEM) The optimized nanosuspension formulations were studied for morphological characters.²⁰ The morphology of the optimised Fexofenadine-loaded solid Lipid nanoparticles was investigated using scanning electron microscopy (SEM). A scanning electron microscope is one of the types of electron microscope that utilizes a focused beam of electrons to scan materials and produce images. Electrons interact with atoms in the sample, producing a mixture of detectable signals that convey information of the composition of the sample and surface topography. SEM images of the created nanoparticles were obtained at room temperature with the help of scanning electron microscope (Carl Zeiss fees model number. Ultra 55 USA) at 100 KX magnifications.²¹

Evaluation of Solid Lipid Nanoparticle Based Gel:

Physical Appearance:

Visual inspection was used to evaluate the prepared solid lipid nanoparticle-basedgels for its colour, odour, transparency, texture, and flocculation. The gel turns opaque when there is the addition of solid lipid nanoparticle dispersion.

In vitro Drug Release:

To ascertain the amount of Fexofenadine HCl released from each formulation using a modified Franz diffusion cell in vitro release tests was conducted. A donor compartment, an acceptor compartment, Dialysis membrane 70, magnetic stirring, a thermostatic water bath, and a sample equipment was used to make Franz diffusion cells.

The Franz diffusion cells were fitted with a dialysis membrane 70 with a pore size of 2.4nm and a molecular weight cut-off of 12,000-14,000. The releasing membrane had a surface area of 3.14 cm2. The receptor medium was 45mL of phosphate buffer saline (PBS) with a pH of 5.5 and was swirled at 700rpm with a magnetic bar to avoid differing concentrations within the acceptor medium and reduce stagnant layers. In the donor compartment, SLN-based gels (equal to 100mg of medication) were inserted. The solution in the receptor side was kept at 37°C 0.5°C throughout the trials.

3-mL of the sample medium was taken from the receiver compartment through the side tube after a predetermined time interval, and the same quantities of freshly produced receptor media were added. A UV-Visible spectrophotometer set to 220nm was used to examine the samples. The release studies weredone three times for each formulation.^21,22

Drug Content:

The total amount of drug in the formulation was calculated by dissolving 1ml of emulsion in 10ml of methanol. The concentration of fexofenadine HCl in each sample was determined by examining the absorbance of the clear supernatant at a maximum wavelength of 220nm. Three trials of each experiment were conducted. By handling a placebo formulation similarly to the sample, the UV absorbance was measured. The total drug content was ascertained using the equation below.^23,24

TDC = concentration × dilution factor × volume of formulation

Spreadability:

By using a laboratory-modified device the Spreadability of the gel formulations was accurately measured. The instrument was made from two glass plates and a pan mounted on a pulley. An excessive amount of gel was applied in the space (10 x10cm²) between the glass slides. Using a 100g weight on the upper glass plate, the formulation was compressed for 5 minutes. The 100g weight was fastened to the pan. The amount of time it took to separate the slides in seconds was used to calculate Spreadability.^25,26

The formula below was used to calculate the Spreadability.

S = M×L/t 

pH:

In order to determine the pH of the gel composition, a digital pH metre was employed. The measurements were recorded on a pH meter after calibrating the electrode with pH 4.0 and pH 7.0 solutions.^27,28

Viscosity:

Using a Brookfield viscometer (Model-DVII) with spindle LV-4 at 25°C and 2°C, the viscosity of the gel was ascertained.^29,30

Homogeneity:

Visual inspection was used to check for sediment or floccules in the prepared nanoparticle-based gel formulation.³¹

RESULTS AND DISCUSSION:

Entrapment efficiency:

The entrapment efficiency of solid lipid nanoparticles is an important characteristic to consider while describing them. Several aspects were changed in order to achieve optimal encapsulation efficiency, including the types and concentrations of lipid and surfactant materials utilized. Table 1 shows the entrapment efficiency of all the manufactured SLN formulations. SLN dispersion entrapment efficacy was determined to be between 81.08 and 93.62%.

The entrapment efficiency of all SLN formulations generated with a greater surfactant content (2%) was higher. Regardless of surfactant type, [F2-90.30 %, F4-87.59%, F6-93.62%, F8-84.68%] this demonstrated that increasing the surfactant content improves the entrapment efficiency. This could be attributed to an increase in drug solubility in lipids when the surfactant concentration rises. The entrapment efficiency of the formulations employing poloxamer407 as a surfactant was lower than the other surfactants, which could be owing to the lower HLB value of Poloxamer 407. As a result, the entrapment efficiency of different SLNs stabilized with different non-ionic surfactants and decreased in the following order: poloxamer188 > poloxamer 407 > Tween 80 > Span 20.

Figure No. 1: Entrapment Efficiency Effect of surfactant on entrapment efficiency 

Fourier Transform Infra-Red (FTIR) Spectroscopy for Drug – Excipient Compatibility:

FTIR was used to record the IR spectrum of pure drug and excipients, as well as a mixture of drug and excipients, and the compatibility of the drug and excipients was determined by comparing the spectra. In the description, the FTIR of all the samples is shown, along with the spectra peaks. The sample included all of the characteristic peaks. The FTIR analysis revealed that Fexofenadine HCl had no interaction with any of the excipients. The FT-IR spectrum of Fexofenadine HCl showed the characteristics absorption bands at 3292.49 (OH stretching), 2929.87 (CH stretching), 2640.55 (OH of carboxylate), 1699.29 (CO stretching), 1450.47, 1319.31 (c=c stretching of aromatic ring), 1163.88 (CO stretching of tertiary alcohol), 1064.71 (CO stretching of secondary alcohol).

Figure No. 2: IR Spectra of Fexofenadine HCl.

Figure No. 3: IR spectra of API and Excipient Zeta potential and particle size distribution

Figure No. 4: Zeta potential of SLN

The particle size of the batches that were prepared was measured. For the SLN batches that were synthesised, particle sizes ranged from 168nm to 737nm, with a zeta potential of -12 to -20 mV. Increased lipid content (GMS) has no effect on particle size, however increasing Poloxamer 188 concentrations reduces particle size. The following diagram shows thezeta potential.

Evaluation parameter of solid lipid nanoparticle-based gel 

Table No. 3: Evaluation of SLN based gel In vitro diffusion study

Evaluation Parameter	0.5% Gel(G1)	1% Gel(G2)	1.5% Gel(G3)
pH	5.56	5.56	5.49
Viscosity(cP)	12480	12356	12658
Spreadability (g.cm/sec)	0.435	0.468	0.321
Homogeneity	Excellent	good	good

Diffusion experiments were conducted in a Franz diffusion cell using phosphate buffer pH 5.5 as the diffusion medium. The diffusion tests lasted six hours. The drug release rates for formulations G1, G2, and G3 were 57.36%, 48.42%, and 41.57%, respectively. A minimum level of drug release was observed in the G3 formulation for up to 6 hours. The swelling of the gel increases as the concentration of Carbopol 934 increases, lowering the medication release rate.

Kinetics modelling of In-vitro drug release:

To determine the drug's release mechanism from the solid lipid nanoparticles, the invitro release data was fitted into a number of release kinetic models.

Table No. 4: R² value from drug release kinetic model of all the formulation

Formulation Kinetic models	F2NG1 (0.5%)	F2NG2 (1%)	F2NG31 (1.5%)
Zero order model	0.9983	0.9756	0.963
First order model	0.8357	0.8983	0.8915
Higuchi model	0.9026	0.8263	0.8022
Korsmeyer-peppas model	0.9106	0.9472	0.9209
Hixson-Crowell model	0.939	0.979	0.9807

Optical microscopy:

Fexofenadine-loaded solid lipid nanoparticles were produced and optimized for optical microscopy, under 100X electron microscope. Ultra-deformable vesicle formulations' microscopic appearance as determined by electron microscopy is shown in Fig no.5.

Scanning electron microscopy:

The surface topography of the nanoparticles was studied using SEM. The produced nanoparticles were found to be spherical in nature.  As shown in Figure No. 6.

Figure No. 5: Optical microscopy of solid lipid nanoparticles under electron microscope

Stability Study:

According to ICH recommendations, the stability analysis of the nanoparticle gels was carried out. According to ICH rules, freshly manufactured formulations were separated into groups and stored under specific conditions. Samples were periodically taken and analysed for different evaluation criteria.

Figure No. 6: SEM of SLN of optimized batch

CONCLUSION:

Solid lipid nanoparticles were prepared by hot homogenization method using a solid lipid of and different polymers. A solid lipid nanoparticle formed by drug and polymer poloxamer 188 in ratio showed highest entrapment efficiency as well as drug release of the medication from the solid lipid nanoparticle formulation. The prepared nanoparticles were used to formulate the nanogel using Carbopol 934. The nano-drug delivery system developed by the hot homogenization method has demonstrated their suitability for a topical route for the treatment of skin allergy. Thus, the studies revealed that the developed system has a great appeal for the convenient treatment of dermatological allergy that may overcome in improving the limitations of the existing drug delivery system.

ACKNOWLEDGEMENT:

We Thanks Dr. Ashish Jain (Principal of Shri D.D. Vispute College of Pharmacy and Research Center) for providing the in valuable support. We would also like to thank Mr. Kedar Bavaskar for his assistance.

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Received on 01.03.2023         Modified on 08.04.2023

Accepted on 29.04.2023   ©AandV Publications All Right Reserved

Res.  J. Pharma. Dosage Forms and Tech.2023; 15(3):151-156.

DOI: 10.52711/0975-4377.2023.00025