Development and evaluation of nanosuspension of famciclovir for ophthalmic application

 Corresponding author: PIYUSH MALVIYA. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Development and evaluation of nanosuspension of famciclovir for ophthalmic application PIYUSH MALVIYA *, MONIKA MAAN NUTAN MIMROT and REVATHI A. GUPTA Institute of Pharmacy, Dr. A.P. J. Abdul Kalam University, Indore, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(02), 236-240 Publication history: Received on 31 December 2024; revised on 07 February 2025; accepted on 10 February 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.2.0154 Abstract Different excipients are used in formulation like Poloxamer-188, PVP K-90, different concentrations. F5 batch has shown the better results in high-speed homogenization Different excipients were shown variation in particle size, DSC study, drug content, entrapment efficiency and in-vitro dissolution study. Optimized formulation was chosen on the basis of results obtained from particle size and entrapment efficiency. The combination of excipients yields nanosuspension with the smallest average particle size and by the transformation of the nanosuspension into the physical stability of this system could be further enhanced. Keywords: Nano Suspension; Famciclovir; Ophthalmic; Evaluation; Viral 1. Introduction 1.1 Nanosuspension Nevertheless, pharmacokinetic studies of BCS class – II drugs showed that they have a low oral bioavailability, which may be due to the poor water solubility of the drug. There are many classical pharmaceutical ways to improve drug dissolution rates such as dissolution in aqueous mixtures with an organic solvent1 [9], the formation of ß-cyclodextrin complexes2, solid dispersions3 and drug salt form4. During last 20 years a new technology, reducing drug particle size, has been developed to increase drug dissolution rate. According to Noyes–Whitney equation, drugs with smaller particle size have enlarged surface areas which lead to increase dissolution velocity. Higher the dissolution rate together with the resulting higher concentration gradient between the gastrointestinal lumen and systemic circulation could further increase oral bioavailability of drugs5. Nanosuspension is a submicron colloidal dispersion of drug particles which are stabilized by surfactants. A pharmaceutical nanosuspension is defined as very finely dispersed solid drug particles in an aqueous vehicle for oral, topical, parenteral or pulmonary administration. The particle size distribution of the solid particles in nanosuspensions is usually less than one micron with an average particle size ranging between 200 and 600 nm6. In nanosuspension technology, the drug is maintained in the required crystalline state with reduced particle size, leading to an increased dissolutionrateand therefore improved bioavailability. An increase in the dissolution rate of micronized particles (particle size < 10 μm) is related to an increase in the surface area and consequently the dissolution velocity. Nanosized particles can increase solution velocity and saturation solubility because of the vapor pressure effect. In addition; the diffusional distance on the surface of drug nanoparticles is decreased, thus leading to an increased concentration gradient. Increase in surface area, as well as concentration gradient, leading to a much more pronounced increase in the dissolution velocity as compared to a micronized product. Another possible explanation for the increased saturation solubility is the creation of high energy surfaces when disrupting the more or less ideal drug microcrystals to World Journal of Biology Pharmacy and Health Sciences, 2025, 21(02), 236-240 237 nanoparticles. Dissolution experiments can be performed to quantify the increase in the saturation solubility of a drug when formulated into a nanosuspension7.The stability of the particles obtained in the nanosuspension is attributed to their uniform particle size which is created by various manufacturing processes. The absence of particles with large differences in their size in nanosuspensions prevents the existence of different saturation solubilities and concentration gradients; consequently, preventing the Oswald ripening effect. Ostwald ripening is responsible for crystal growth and subsequently formation of micro-particles. It is caused by a difference in dissolution pressure/saturation solubility between small and large particles. Molecules diffuse from the higher concentration area around small particles which have higher saturation solubility to an area around larger particles possessing a lower drug concentration. This leads to the formation of a supersaturated solution around the large particles and consequently to drug crystallization and growth of the large particles. Table 1 Formulation consideration for Nanosuspension Excipients Function Examples Stabilizers Wet the drug particles thoroughly, prevent Ostwald’s ripening and agglomeration of nanosuspensions, providing a steric or ionic barrier Soya Lecithins, Poloxamers188/407, Polysorbate 80, HPMC E-15/E-50, PVP K-25/K-30 Cosurfactants Influence phase behavior when microemulsions are used to formulate nanosuspensions Bile salts, Dipotassium Glycyrrhizinate, Transcutol, Ethanol, Isopropanol Organic solvent Pharmaceutically acceptable less hazardous solvent for preparation of formulation. Methanol, Ethanol, Chloroform, Isopropanol, Ethyl acetate, Ethyl formate, Butyl lactate, Triacetin, Propylene carbonate, Benzyl alcohol. Other additives According to the requirement of the route of administration or the properties of the drug moiety Buffers, Salts, Polyols, Osmogens, Cryoprotectant etc. 2. Material and Method 2.1 Material Table 2 List of Materials Sr. No. List of Chemicals Gifted by 1 Famciclovir Srijan Pharma, Baddi. 2 Poloxamer 188 Srijan Pharma, Baddi. 3 Polyvinyl alcohol Srijan Pharma, Baddi. 4 PVP K 90 Srijan Pharma, Baddi. 5 SLS Srijan Pharma, Baddi. 6 Mannitol Srijan Pharma, Baddi. Solvents 7 Methanol(AR grade) S.K. Traders, Indore 8 Ethanol (AR grade) S.K. Traders, Indore 9 Acetone (AR grade) S.K. Traders, Indore World Journal of Biology Pharmacy and Health Sciences, 2025, 21(02), 236-240 238 2.2 Methods • Preformulation studies of drug o Colour, odour and appearance o UV analysis o Solubility o Melting point o FTIR • Formulation of Nanosuspension by using High speed homogenization process • Selection of optimized formulation • Evaluation of Optimized Formulation o Particle size o Entrapment efficiency (%) o Redispersibility of nanosuspension o Scanning electron microscopy o In-Vitro Drug Release Study o Stability Studies 3. Result and Discussion 3.1 Organoleptic Properties of Drug Table 3 Organoleptic Properties of Drug Sr. no. Parameter Description 1 Color White to off white 2 Odor Odorless 3 Appearance Non-hygroscopic white or whitish crystalline powder 3.1.1 Solubility Studies The solubility in Ethanol, pH 7.4 and Distilled water, while optimized formulation is completely soluble in methanol, and poorly soluble in water, Ethanol, pH 7.4. of pure drug Famciclovir is completely soluble in methanol. 3.1.2 Identification Of Drug Identification of artemether and lumefantrine is carried out by FTIR Spectrophotometry. Table 4 Identification of Drug by FTIR Spectrophotometry Sr. No. Observed peaks (cm-1) Reported peaks (cm-1) Interpretation of chemical group Intensity 1 1627.01 1620-1520 C= O Phenyl Medium 2 1389.76 1454-1358 C-H Strong 3 1182.40 1180-1185 C-O Strong 4 893.07 991-802 -CH Strong 5 3441.12 3400-3700 O-H Medium-strong World Journal of Biology Pharmacy and Health Sciences, 2025, 21(02), 236-240 239 Figure 1 For FTIR 3.1.3 Differential scanning calorimetry (DSC) Figure 2 DSC graph of Famciclovir 3.1.4 In-Vitro Drug Release Study Table 5 Drug release study Sr.No Time (min) % Cumulative Drug Release 1 0 0 2 15 2.30 3 30 4.11 4 45 24.87 5 60 35.95 6 120 68.20 7 180 94.20 World Journal of Biology Pharmacy and Health Sciences, 2025, 21(02), 236-240 240 Figure 3 In vitro release study of the Optimized nanosuspension formulation 3.1.5 Stability study Table 6 Stability Study Sr. No. Parameter 0 Month 1 Month 2 Month 3 Month 1 Particlesize (nm) 203.2 ± 0.45 204.7 ± 0.12 205.1 ± 0.3 206.6 ± 0.2 2 % Entrapment Efficiency (EE %) 90.6 ± 0.5 88.2 ± 0.30 84.2 ± 0.4 82.2 ± 1.0 4. Conclusion Results conclusively prove that Famciclovir nanosuspension prepared by high-speed homogenization method. Different excipients are used in formulation like Poloxamer-188, PVP K-90, different concentrations. F5 batch has shown the better results in high-speed homogenization Different excipients were shown variation in particle size, DSC study, drug content, entrapment efficiency and in-vitro dissolution study. Optimized formulation was chosen on the basis of results obtained from particle size and entrapment efficiency. The combination of excipients yields nanosuspension with the smallest average particle size and by the transformation of the nanosuspension into the physical stability of this system could be further enhanced. Compliance with ethical standards Disclosure of conflict of interest For the Institutional growth of the authors. References [1] Makoid CM, Vuchetich PJ, Banakar UV (1999) Basic Pharmacokinetics. 1st Edition. [2] Aulton ME (2007) Pharmaceutics - The Science and Dosage Form Design. 2nd Edition.Churchill Livingstone, New York. [3] Chow SC and Liu JP (2009) Design and Analysis of Bioavailability and Bioequivalence Studies. 3rd Edition. CRC Press, Taylor and Francis Group, Boca Raton. [4] Russell TL, Berardi RR, Burnet JL, O’Sullivan TL, Wagner JG and Dressman JB, 1994, pH-related changes in the absorption of Dipyridamole in the elderly.