Improvement of dissolution characteristics of slightly soluble drug by solid dispersion technique- Practical

 
IMPROVEMENT OF DISSOLUTION CHARACTERISTICS OF SLIGHTLY SOLUBLE DRUG BY SOLID DISPERSION TECHNIQUE

AIM:

To improve dissolution characteristics of slightly soluble drug by solid dispersion technique.

 THEORY:

 Solid dispersion is one of the methods, which was most widely and successfully applied to improve the solubility, dissolution rates and consequently the bioavailability of poorly soluble drugs. The solid dispersion is based on the concept that the drug is dispersed in an inert water-soluble carrier at solid state. When the solid dispersion comes to contact with the aqueous solution, the inert carriers dissolves and the drug is released, the increased surface area produces a higher dissolution rate thus increasing the bioavailability of the poorly soluble drugs. The carriers should be freely water soluble, non-toxic, inert, thermally stable and chemically compatible with drugs. Several water soluble carriers such as methyl cellulose ,hydroxy ethyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, urea, lactose, dextrose, citric acid, succinic acid polyvinyl pyrrolidone (PVP) and polyethylene glycols 4000 and 6000 are used as carriers for making solid dispersion. The term solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles (clusters) or in crystalline particles.

 PROCEDURE:

Preparation of  PEG 4000-Paracetamol Solid Dispersion:

a)Preparation of physical mixture

The physical mixture ofParacetamol(800mg)- PEG 4000(1600mg) were prepared in 1:2 ratio by mixing continuously accurately weighed amounts of drugs and carrier with the help of a spatula in a glass mortar.

 b) Preparation by kneading method

The required amount of Paracetamol(800mg)and carrier(1600g) in 1:2  ratio were wetted with sufficient volume of methanol and kneaded thoroughly for 30 mins in a glass mortar. The solid dispersion  formed was dried under vacuum for 24 hrs. Dried powder was passed through sieve no. 30 and stored in self sealing cover  in desiccator until further evaluation.

EVALUATION:

Solubility :

1) The pH solubility profile ofprepared solid dispersion , physical mixture and drug was determined at 37 ±1⁰C in aqueous media with pH 5.8.

2) Standard buffer solution of pH 5.8 was prepared under standard condition.(water made to buffer solution)

3) Then the pH of the buffer prepared was found out using pH meter.

4) 60mg of solid dispersion, 60mg of physical mixture and 20mg of drug (Paracetamol) was taken in 10ml volumetric flasks and make upto 10ml using  5.8 buffer.

5)  Then the volumetric flasks were placed in orbitary shaker   for 1 hr at 37⁰C.

6) After 1hr the solution in the volumetric flasks were filtered and the filtered solutions of solid dispersion, physical mixture and the drug were analysed using UV spectrometer.

7)    From the absorbance value obtained the concentration present in the sample can be determined by using standard calibration curve and compared.

 

Differential scanning calorimeter:

Differential scanning calorimetry (DSC) monitors heat effects associated with phase transitions and chemical reactions as a function of temperature and is a very informative method in physical characterisation of a compound. In Differential Scanning Calorimetry, the difference in heat flow to the reference  and a sample  at the same temperature, is recorded as a function of temperature. The reference is an inert material such as alumina or just an empty aluminium pan. The temperature of both the sample and reference are increased at a constant rate.

Procedure:

0.42g of the sample was loaded in aluminium pans.

Both the reference pan and the sample pan was loaded into the instrument.

The sample is analysed and thermogram was obtained as per standard operating procedure.

The thermogramof sample obtained was compared with thermogram of paracetamol and PEG 4000)

From the comparison compatability studies were made. 

REPORT:

Paracetamol drug comes under BCS class 2. Hence improvement of solubility is needed and chosen for this experiment. From the article reviews PEG 4000 is mostly used compared to other molecular weight carriers. Because of the hydrophilic nature of the PEG 4000 it has been chosen for solid dispersion. From the performed experiment the ratio of drug present in solid dispersion: physical mixture: drug is 58.7%: 34.6%: 38.45%.From the solubility profile obtained on comparing solid dispersion, drug and physical mixture it is evident that solid dispersion was found to be 1.696 folds more that physical mixture and solid dispersion was found to be 1.52 folds more than pure drug. Hence the solubility of solid dispersion is comparatively more than the physical mixture and the drug. In case of differential scanning calorimetry based on melting point of paracetamol and PEG 4000 we got two peaks in exothermic reaction region at 169°c and 60°c respectively. So from the peak obtained there is only physical interaction than any other interaction. 

OUTCOME:

1:4 Ratio of Paracetamol and PEG-4000 may be considered as a suitable ratio for developing the formulation to improve its solubility profile for achieving bioavailability of Paracetamol.