Solid Dispersion to enhance solubility of Fenofibrate:-

Preparation of Solid Dispersion:

A solid dispersion is the dispersion of one or more active ingredients in an inert carrier at

solid-state prepared by melting (fusion), solvent or the melting-solvent method, where the

active ingredients could exist in finely crystalline, solubilized, or amorphous states". The

method of preparation of solid dispersions was based on the solvent evaporation

method. In the solvent evaporation method of preparation, Fenofibrate, the drug solution was

prepared by using drug (40 mg), solvent (Ethanol: Methanol, 4:5) and polymer (PEG 6000,

PVP, Poloxomer 188, Poloxomer 407, HPMC 6cps and Mannitol. The polymers have been

used as carriers with Fenofibrate in various (Drug:Carrier) ratio such as, 1:1, 1:3, 1:5, 1:7 and

1:10 and finally the solvent was evaporated by a dryer at 50-60°C. The solid dispersions were

withdrawn from vials, crushed in mortar and pestle then passed through sieve (first 40 mesh

and the 80 mesh). Then the resulted samples were weighed and transferred in fresh vials with

proper labeling. After preparation solid dispersions were kept in the dessicator.

In vitro Dissolution Study of Solid Dispersion

The release rate of fenofibrate from solid dispersion were carried out in dissolution test

apparatus Paddle type II (Electrolab, India) at rotation speed of 75 rpm was used for the

study. Dissolution of the drug and solid dispersion was carried out on an equivalent of 40 mg

of the Fenofibrate in 900 ml 0.75% sodium lauryl sulfate (SLS) in distilled water as

dissolution media and the temperature was maintained at 37°C+0.5°C. At different interval

(5-60 min) samples were collected (US FDA Dissolution Methods) and assayed by UV

spectrophotometer. To increase the reliability of the observations, the dissolution studies

were performed in triplicate.

Characterization of Drug & Solid Dispersion by FT-IR Study

Fourier Transform- Infra Red spectroscopy (FT-IR) spectra of pure Fenofibrate and prepared

solid dispersions were recorded on Shimadzu FT-IR. Potassium bromide pellet method was

employed and background spectrum was collected under identical situation. The powdered

sample was intimately mixed with dry powdered potassium bromide. The mixture was then

compressed into transparent disc under high pressure using special dies. The disc was placed

in IR spectrophotometer using sample holder and spectrum was recorded. Each spectrum was

derived from single average scans collected in the region 400-4000 cm'at spectral resolution

of 4cm' and ratio against background interferogram. Spectra were analyzed by software

supplied by Shimadzu. In this study, potassium bromide disc method was employed.

RESULT AND DISCUSSION

In Vitro Dissolution Study of solid dispersion

The present study was aimed to observe release pattern of drug from the solid dispersion by

using different carriers which generally change the nature of the insoluble drug to amorphous

form and help to enhance the rate of drug release. The complete comparative study of pure

Fenofibrate and prepared formulations of solid dispersions were observed where the rate of

dissolution was found increased in all the solid dispersions compared to pure Fenofibrate.

Solid dispersions with all the carrier used showed their highest release (65.77% to 93.74%) in

the maximum drug-carrier ratio of 1:10 (Figure 1). Solid dispersions prepared with

Poloxamer 188 showed fastest and the maximum release (93.74%) among all (Figure 2) and

then formulations with PVP, HPMC, Poloxamer 407, Mannitol showed their release

enhancement (82.87%, 76.50%, 88.14%, 88.21% and 65.77% respectively). This is to be

noted that micronized pure Fenofibrate showed its release of only 23.60% after 60 minutes of

dissolution study

World Journal of Pharmaceutical Research