Development and Characterization of Solid Dispersion System for Solubility Enhancement of Fenofibrate

Fenofibrate is an anti-hyperlipidemic drug that belongs to fibrate class. It helps to reduce elevated plasma concentration of triglycerides and LDL. Generally, it is more effective drug as compare to other fibrates. Fenofibrate is included in BCS Class II drugs resulting it shows low bioavailability.¹⁴ The enhancements of oral bioavailability of poorly water-soluble drugs often show poor bioavailability because of low and erratic levels of absorption. Drugs that undergo dissolution rate limited, in gastrointestinal absorption and it shows improved dissolution and bioavailability by reduction in particle size. However, drugs often lead to aggregation and agglomeration of particles, which results in poor wettability^14-5. Solid dispersions of poorly water-soluble drugs with water-soluble carriers have been reduced the incidence of these problems and enhanced dissolution. The development of solid dispersions as a practically viable method to enhance bioavailability of poorly water-soluble drugs overcame the limitations of previous approaches such as salt formation, solubilisation by co solvents, and particle size reduction, solvent evaporation method. Studies revealed that drugs in solid dispersion need not necessarily exist in the micronized state⁵. A fraction of the drug might molecularly disperse in the matrix, thereby forming a solid dispersion. When the solid dispersion is exposed to aqueous media, the carrier dissolves and the drug releases as fine colloidal particles. Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. Fenofibrate needs to improve its oral bioavailability, solubility, and dissolution rate¹³. The method have been used to increase the solubility, dissolution rate, and bioavailability of poor water soluble medicines, including solid dispersion. solvent evaporation method. This method used to improving the solubility, dissolution rate, and bioavailability of poorly soluble Fenofibrate medicine. It is a straightforward, industrially useful method¹⁴. The goal of the current research project was to create Fenofibrate tablets with a solvent evaporation method approach to increase solubility and dissolution rate¹².

Solid Dispersion:

Solid dispersion helps break the drug into very fine particles, increasing its surface area and improving its dissolution rate, as described by the Noyes-Whitney equation. Although reducing particle size to the nano level can speed up dissolution, it cannot increase the drug’s solubility beyond its natural limit in intestinal fluids. To overcome this, solid dispersion is an effective technique for enhancing the solubility and absorption of poorly water-soluble drugs. It can increase the drug concentration at the site of absorption and even create a temporary supersaturated state, which boosts bioavailability. Solid dispersion remains a popular area of research because it is versatile and suitable for different dosage forms, especially tablets are most commonly used form for oral drug delivery.¹⁴

MATERIALS:

Fenofibrate API from Balaji Drug Limited, Mumbai, other laboratory chemicals such as chloroform, Ethanol, Acetone, and Excipients PVP-K30, HPMC E15, Microcrystalline cellulose, Croscarmellose Sodium, Aerosil, Sodium lauryl sulphate, Magnesium stearate are available at Institute.

Preformulation studies

An investigation of physical and chemical properties of a drug substance alone is defined as “Pre?formulation.”

OBJECTIVE

It generates useful information to the formulator that is useful in developing stable and bio available dosage forms.

These are

1. Organoleptic properties
2. Solubility studies.

Organoleptic properties

Colour, Odour, taste, appearance of the drug play an important role in the identification of sample of above all properties should be recorded in descriptive terminology¹⁶.

Solubility studies

The solubility of Fenofibrate was tested in ethanol, methanol, and water. About 10 mg of the drug was added to 5 mL of each solvent in separate test tubes. After vigorous shaking, the mixtures were visually observed. Fenofibrate showed complete solubility in ethanol and methanol. It remained practically insoluble in water, with undissolved particles visible.

Determination of melting point

Melting point of Fenofibrate was determined by capillary method. Observed values compared with reported value. This method involves placing the sample in a capillary tube and running an experiment that will heat the sample until it reaches melting point. The melting point can then be recorded.

UV Visible Spectroscopy

In order to create a standard stock solution of 100 µg/ml, 10 mg of precisely weighed Fenofibrate was dissolved in 100 ml of ethanol in a 100 ml volumetric flask. The volume was then increased to 100 ml with ethanol. 2.5 milliliters of the standard stock solution were pipetted into a 10-milliliter volumetric flask. Water was added to get the volume up to 10 ml. Between 200 and 400 nm, the resultant solution, which contained 10 µg/ml, was scanned.

FTIR (Fourier Transform Infra-Red Spectroscopy)

Infrared spectroscopy was used to detect chemical interactions between Fenofibrate and excipients during storage. The IR spectra of pure drug and physical mixtures were compared for any changes. Samples from the stability chamber were analyzed by mixing drug and excipients with KBr in a 1:1 ratio. Pellets were prepared and scanned in the 4000–400 cm?¹ range using an FTIR spectrophotometer. Variations in spectra indicated possible interactions.

Differential Scanning Calorimetry (DSC)

The differential scanning calorimetric technique was used to do a thermal examination of Fenofibrate with all excipients. An device called the Shimadzu DSC-60plus was used to evaluate the samples. All excipients and a sample equal to around 10 mg of fenofibrate were heated in open aluminium pan at a rate of 100 C/min. conducted over a temperature range of 30 to 3200C to a nitrogen flow of 2-bar pressure. Drug melting point to be examined and checked.

Preparation of Fenofibrate tablet by solvent evaporation method

The Formulation of Fenofibrate tablet by solvent evaporation method, the first step is to choose a suitable solvent that can easily dissolve both the drug and the polymer. Ethanol is selected for this process because it is volatile and effectively dissolves both Fenofibrate and the chosen hydrophilic polymers, such as PVP K30, HPMC E15. In the next step, accurately weighed quantity of Fenofibrate and PVP K30, HPMC E15 are added to a sufficient quantity of ethanol. The mixture is stirred continuously until both the drug and polymer completely dissolve, forming a clear and homogeneous solution. Once the solution is ready, the ethanol is gradually evaporated by gentle heating using a water bath at around 40–50°C. As the solvent evaporates, it leaves behind a solid dispersion of Fenofibrate within the polymer matrix. To ensure complete removal of any residual solvent, the solid mass is further dried in a vacuum oven or desiccator. After drying, the solid residue is collected and pulverized into a fine powder using a mortar and pestle. The powder is then passed through a 60# sieve to achieve uniform particle size and mix the all excipients for tablet compression.

Experimental Design

The current Formulation optimization study were performed using Design Expert® Software (Design Expert trial version 12; Stat-Ease). Box Behnken design was applied for the development of the formulation of Fenofibrate tablet by considering 3 factors and 3 levels (high, low). PVP K30, HPMC, and MCC considered as independent factors and drug release and compressibility index is dependent variables. Because to found best optimization batch in research. The level of all autonomous factors to be chosen based on preliminary trials.

Table 1: Composition of independent variables and their levels for the preparation of Fenofibrate tablet.

Table 2: 3³ full factorial design for formulation designed using Stat-Ease Design Expert® soft-ware (Version 12)