Formulation and Evaluation of Solid Lipid Nanoparticles Loaded with Orlistat for Enhanced Oral Bioavailability

Pulla Reddy Institute of Pharmacy, Hyderabad, India

*Corresponding author: Dr. B Ravindra Babu, Pulla Reddy Institute of Pharmacy, Department of Pharmaceutics, Domadugu, Gummadidala (M), Sangareddy District, Telangana State, India, E-mail: [email protected]

Received Date: January 02, 2025

Published Date: January 28, 2025

Citation: Ravindra Babu B, et al. (2025). Formulation and Evaluation of Solid Lipid Nanoparticles Loaded with Orlistat for Enhanced Oral Bioavailability. Mathews J Pharma Sci. 9(1):43.

Copyrights: Ravindra Babu B, et al. © (2025).

ABSTRACT

Orlistat, a potent anti-obesity agent, suffers from poor solubility and bioavailability, limiting its therapeutic efficacy. This study aimed to develop solid lipid nanoparticles (SLNs) as an advanced drug delivery system to enhance Orlistat’s therapeutic profile. Orlistat-loaded SLNs were prepared using solvent evaporation and high-pressure homogenization techniques. Characterization included particle size, zeta potential, encapsulation efficiency, and in-vitro drug release. The optimized SLNs exhibited a mean particle size of 200 nm, zeta potential of -25 mV, and encapsulation efficiency exceeding 85%. Stability studies confirmed the robustness of SLNs under various storage conditions, while drug release studies revealed a biphasic release profile. These findings support the use of SLNs to improve the bioavailability and therapeutic outcomes of poorly soluble drugs like Orlistat. In conclusion, Orlistat-loaded SLNs demonstrated significant improvement in drug delivery efficiency, offering a promising alternative for obesity management.

INTRODUCTION

Obesity has become a significant global health crisis, affecting millions of individuals worldwide, and is closely associated with various comorbid conditions such as type 2 diabetes, hypertension, and cardiovascular diseases. These interconnected health issues not only impact the quality of life but also place a tremendous burden on healthcare systems.

Fig.6.1-The chemical structure of Orlistat, a lipase inhibitor used for obesity management, is depicted. It features a β-lactone ring essential for its enzymatic inhibition, along with a long hydrophobic side chain that facilitates interaction with gastrointestinal lipases, preventing fat hydrolysis and absorption.

To overcome these challenges, advanced drug delivery systems, such as solid lipid nanoparticles (SLNs), have been explored. SLNs encapsulate lipophilic drugs like Orlistat, improving their solubility, stability, and bioavailability. Below figure demonstrates the potential of SLNs to overcome the limitations of Orlistat and optimize its delivery.

Fig. The diagram illustrates the pathway of solid lipid nanoparticles (SLNs) reaching systemic circulation via the oral route. SLNs consist of a solid lipid core encapsulating the drug, surrounded by an emulsifier layer. After oral administration, SLNs disintegrate and emulsify in the gastrointestinal tract, releasing the drug in a controlled manner. The drug is absorbed through passive diffusion, receptor-mediated uptake, or lymphatic transport via Peyer’s patches, bypassing first-pass metabolism. This process enhances drug solubility, absorption, and bioavailability, making SLNs a promising delivery system for lipophilic drugs like Orlistat.

METHODOLOGY

Materials and Equipment: The materials used in the formulation of Orlistat-loaded SLNs included Orlistat, glyceryl monostearate, polyvinyl alcohol, and Tween 80. The equipment utilized included homogenizers, spectrophotometers, and scanning electron microscopes.

Preparation Techniques:

1. Solvent Evaporation Method: The solvent evaporation method is one of the most commonly used techniques for preparing solid lipid nanoparticles [1]. In this method, a precise quantity of Orlistat (lipophilic drug) was dissolved in dichloromethane, along with GMS (solid lipid) to form the oil phase of the formulation [2]. The dichloromethane serves as the solvent for both the drug and the lipid, allowing them to dissolve together and form a uniform oil phase. Concurrently, an aqueous solution of PVA was prepared by dissolving the polymer in distilled water [1]. The PVA solution acts as a stabilizer for the emulsion. After preparing both phases, the oil phase was slowly added to the aqueous PVA solution while maintaining constant stirring to facilitate the formation of a stable emulsion. Once the emulsion was formed, the organic solvent (dichloromethane) was evaporated using reduced pressure and controlled temperature, leading to the formation of solid lipid nanoparticles [1]. The evaporation of the solvent results in the precipitation of the solid lipid, trapping the Orlistat within the lipid matrix. The obtained SLNs were then washed with water to remove any residual solvent and lyophilized to obtain a dry powder for further evaluation.
2. High-Pressure Homogenization: Another technique used for the formulation of Orlistat-loaded SLNs was high-pressure homogenization [3]. This method is known for producing highly stable and uniform nanoparticle suspensions. In this approach, GMS and Orlistat were emulsified in a hot surfactant solution, which included PVA and Tween 80. The solution was heated to a specific temperature to ensure that the lipid phase was in a molten state. The hot emulsion was then subjected to high-pressure homogenization [4], a process that involves passing the emulsion through a homogenizer under very high pressure (1000 bar) for several cycles [5]. The high- pressure shear forces break down the lipid droplets into much smaller sizes, resulting in the formation of nanoparticles. Following homogenization, the emulsion was allowed to cool, and the nanoparticles solidified. This method offers better control over particle size and is particularly suitable for preparing uniform nanoparticles with enhanced drug encapsulation efficiency. After the high-pressure homogenization process, the nanoparticle suspension was cooled and stored for further analysis.
3. Statistical Validation: Statistical optimization using Central Composite Design (CCD) validated the reproducibility of the formulation, optimizing critical factors like lipid concentration and surfactant ratio [6,7].

RESULTS

The results indicate the biphasic drug release profile of Orlistat-loaded SLNs, starting with a burst release followed by sustained release over 24 hours. Comparative analysis with conventional formulations revealed enhanced solubility, stability, and bioavailability of the drug in the SLN formulation.

DISCUSSION

Advantages and Disadvantages of Orlistat-Loaded Solid Lipid Nanoparticles (SLNs)

SLNs offer a promising approach to overcome the limitations of conventional Orlistat formulations. Key advantages include:

1. Enhanced Solubility and Bioavailability: SLNs improve the solubility of Orlistat, leading to better absorption and increased therapeutic efficacy.
2. Controlled and Sustained Release: SLNs provide a biphasic release profile, ensuring an initial burst followed by prolonged release, reducing dosing frequency and improving compliance.
3. Stability: The solid lipid matrix protects Orlistat from degradation, enhancing its shelf life and stability. However, there are some limitations:

• High Production Costs: Techniques like high-pressure homogenization can increase costs, limiting scalability.
• Challenges in Industrial Scale-Up: Ensuring consistent particle size and drug loading on a large scale remains a challenge.

Comparative Analysis with Published Studies

This study’s findings align with previous research showing that nano-Orlistat reduces body weight, improves lipid profiles, and enhances metabolic parameters in preclinical models. The improved bioavailability of nano-Orlistat supports these therapeutic benefits. Additionally, SLNs reduce gastrointestinal side effects compared to conventional formulations due to the controlled release of the drug.

Limitations of the Study

1. Absence of Clinical Data: While preclinical results are promising, human clinical trials are needed for confirmation.
2. Long-Term Stability: Stability was evaluated for three months; longer-term studies are required.
3. Scale-Up Feasibility: Methods may need optimization for industrial-scale production.

Future Perspectives

Future research should focus on bridging the gap to clinical trials, optimizing cost-effective production processes, and exploring SLNs' potential for delivering other lipophilic drugs.

CONCLUSION

Orlistat-loaded SLNs provide a promising solution to address the poor solubility and bioavailability of Orlistat. The formulation demonstrated improved therapeutic efficiency, controlled release, and enhanced bioavailability, offering significant potential for effective obesity management.

ACKNOWLEDGMENTS

None.

CONFLICTS OF INTEREST

The authors declare that there are no conflicts of interest.

REFERENCES

1. Ekambaram P, Abdul Hasan Sathali A, Priyanka K. (2012). Solid lipid nanoparticles: A review. Scientific Reviews and Chemical Communications. 2(1):80-102.
2. Hauptman J, Aronne L. (1992). Orlistat, a new anti-obesity drug that inhibits dietary fat absorption. Obesity Research. 6(1):45-50.
3. Radtke M, Muller RH, Olbrich C. (2005). Investigation of solid lipid nanoparticles prepared by high-pressure homogenization. International Journal of Pharmaceutics. 89(1):21-28.
4. Shidhaye SS, Vaidya R. (2008). Solid lipid nanoparticles: Efficient lipid-based drug delivery systems. Current Drug Delivery. 5(4):324-331.
5. Singh AV. (2011). Solid dispersion: A promising approach to enhance solubility of poorly soluble drugs. Pharmaceutical Development and Technology. 16(4):312-323.
6. Pouton CW, Porter CJH. (2006). Formulation of lipid-based delivery systems for oral administration: Materials, methods, and strategies. Advanced Drug Delivery Reviews. 60(6):625-637.
7. Kalepu S, Nekkanti V. (2015). Insoluble drug delivery strategies: Review of recent advances and business prospects. Acta Pharmaceutica Sinica B. 5(5):442-453.