Nanosuspension: A Novel Approach for The Treatment of Hyperlipidaemia

Abstract

Hyperlipidaemia is a condition characterized by increased levels of lipids in the bloodstream, which can lead to cardiovascular diseases such as stroke. The medications used to treat hyperlipidemia include statins, fibrates, and cholesterol absorption inhibitors, all of which have low water solubility, dissolution, and bioavailability. To address the issue of poor aqueous solubility, these BCS class II drugs often undergo nanosuspension formulation. Nanosuspensions, which are colloidal dispersions of nanosized drug particles, present a promising method for enhancing the pharmacokinetic characteristics of poorly water-soluble drugs. By reducing particle size to between 100 and 600 nm or converting the crystalline form of the drug into an amorphous form, nanosuspensions exhibit a high dissolution rate. During the preparation of nanosuspensions, stabilizers play a crucial role in reducing particle size and preventing the aggregation of drug particles.

Keywords

Introduction

Table No. 1: MOA & Limitations of treatment of hyperlipidaemia

Preparation methods of nanosuspensions; ^4,5

In the preparation methods of Nanosuspensions, there are Bottom-Up technology, Top-Down technology, and Combination Technology.

• Bottom-Up technology; In this approach drug is dissolved in a solvent phase (Methanol, Ethanol, Acetone, etc) and then precipitated as nanoparticles in the presence of an anti-solvent (water). In Bottom-Up techniques, there are Solvent-Anti-Solvent, Supercritical fluid, and Lipid emulsion methods.
• Top-Down technology; In this approach drug will become nanosized from large particles using mechanical forces. In the Top-down technique, there are Media milling method, High-pressure homogenization, nanoedge, and Nanopure methods.
• Combination technique; It integrates both Bottom-Up (Precipitation) and Top-down (High pressure homogenisation) approaches

Bottom-up technique; ⁴

Solvent-anti-solvent Method- This method comes under the Precipitation method. In this method, the drug is dissolved in an organic solvent phase and the stabilizer is dissolved in the aqueous phase. After dissolving the boh phases solven phase is added to the aqueous phase in a drop-by-drop manner with continuous stirring. After the stirring, the formulation undergo sonication for reducing the particle size.

Table No. 3: Advantages and Disadvantages of solvent Solvent-Solvent Method

Top-down technique; ⁵

Media milling method: This method works on the high shear media mill. The chamber contains water, Drug, stabilizer, and milling media (glass + zirconium oxide + resins). This chamber rotates at high speed for  2 to 5 days to break down the particle size. Her some of the advantages and disadvantages of the media milling method

Table No. 4: Advantages and Disadvantages of Media Milling

High pressure homogenization method; In this method, there are mainly 3 steps. In the 1^st step, the drug is dispersed into stabilizer solution, and this solution is homogenized in high pressure and finally homogenized at high pressure for 15 to 25 cycles until to get the desired nano-sized particles and. In this method, there are Homogenization in Aqueous media, in Non-aqueous media, and Nanoedge. Here are some of the advantages and disadvantages of the HPH method

Table No. 5: Advantages and Disadvantages of the HPH Method

Combined techniques; ⁵

Emulsion diffusion method; The Drug and stabilizer are dissolved in a suitable solvent, and the stabilizer is dissolved a water. Add the solvent phase into to aqueous phase with continuous phase under ultrasonication for reducing the droplet size. Add a large amount of water and let the solvent evaporate in the solution.

Table No. 6: Advantages and Disadvantages of Emulsion Diffusion

Figure 1: Flow chart of the preparation of nanosuspension

Excipients in the preparation of nanosuspension ⁶

Table no 7 Excipients in Nanosuspensions

Evaluation parameters of nanosuspensions;

The evaluation parameters of nanosuspension are

• Particle size and Poly dispersity Index
• Zeta potential
• Drug content
• Drug entrapment efficiency
• Saturation solubility
• Scanning Electron Microscopy
• Transmission electron microscopy
• In vitro or Dissolution studies
• In vivo studies

Particle size analysis ^5,6: Particle size affects the Physicochemical properties like solubility and dissolution rate. To analyse the particle size of the formulation Particle size analyser (Zetasizer) is used, and the particle size should be in the 100 to 600nm range.

PDI ⁴; Poly Dispersity Index is to know the uniform particle sizes, and it should be <0.1 to get the monodisperse particles, and the Dynamic Light Scattering evaluates it

Zeta Potential⁷; It is to know the stability of the suspension and to know the electrostatic forces between the dispersed particles, and the minimum zeta value is 30 mV

Drug Content: The weighed amount of the formulation is subjected to high-speed centrifugation to separate drug-loaded nanoparticles. After collecting the supernatant liquid, add a suitable solvent and sonicate the mixture. Then, filter the solution and measure the absorbance using UV-visible spectrophotometry, comparing it with the calibration curve. 

Drug content (%) = (amount of drug estimated/Theoretical drug content) X 100

Drug Entrapment Efficiency: Centrifuge the formulation at high speed to separate the free drug. Collect the supernatant liquid and filter it. After filtration, measure the absorbance by UV-visible spectrophotometry and compare it with a calibration curve.

EE = Total drug- Free drug/Total drug

Saturation Solubility^{4, 5}; It is necessary to evaluate the drug's saturation solubility in various physiological buffers and at various temperatures, utilizing techniques outlined in the literature. Assessment of saturation solubility helps in figuring out the formulation's in vitro behaviour

SEM: Scanning Electron Microscopy; It is used to determine the shape and morphological structures of the suspended particles

In Vitro Studies; It is performed in a basket or paddle type dissolution apparatus with a suitable buffer and at a temperature of 37 degrees Centigrade with paddle speed 50 rpm.

REFERENCES

1. Tripathi KD. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. p. 636–42.
2. Brunton LL, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Medical; 2011. p. 902.
3. Mohan H. Textbook of Pathology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. p. 1055.
4. Geetha G, Poojitha U, Khan AA. Various techniques for preparation of nanosuspension. Int J Pharm Res Rev. 2014;3(9):30–7.
5. Shahidulla SM, Miskan R, Sultana S. Nanosuspensions in pharmaceutical sciences: A comprehensive review. Int J Health Sci Res. 2023;13(7).
6. Komasaka T, Fujimura H, Tagawa T, Sugiyama A, Kitano Y. Practical method for preparing nanosuspension formulations for toxicology studies in the discovery stage. Chem Pharm Bull (Tokyo). 2014;62(11):1073–82.
7. Kamble S, Agarwal A. Advances in nanopharmacy: Techniques for preparing ezetimibe polymeric nanosuspension through lyophilization. Bharati Vidyapeeth Med J. 2025;5(1).
8. Abo-Zalam HB, Abdalsalam RA. Revolutionizing hyperlipidemia treatment: Nanoencapsulated CoQ10 and selenium combat simvastatin-induced myopathy and insulin resistance in rats. Adv Pharm Bull. 2024;14(12):364–77.
9. Ghyadh BKK, Al-Khedairy EBH. Solubility and dissolution enhancement of atorvastatin calcium using phospholipid solid dispersion technique. Iraqi J Pharm Sci. 2023;32.
10. Rani RR, Banu Z, Rahman A. Comprehensive review of hyperlipidemia: Pathophysiology, diagnosis and management.