INTRODUCTION:

Paracetamol^{1, 2} is a non steroidal analgesic and antipyretic agent with minimal side effects. Chemically it is 4-hydroxy acetanilide. It is a potent antipyretic and equianalgesic with aspirin in therapeutic doses, commonly used in the conditions like headache, dysmenorrhoea. It is the most frequently prescribed antipyretic agent. It is white crystalline powder, freely soluble in ethanol (95%) and in acetone; sparingly soluble in water, very slightly soluble in dichloromethane and in ether. The drug suffers from poor bioavailability due to its poor aqueous solubility. Aqueous solubility plays and important role in the dissolution of drug in the gastrointestinal fluid. Various approaches for increasing the aqueous solubility of drugs have been reported in literature. The use of carriers as cosolvents is one such approach. The present study investigates the use of various carriers that can enhance the solubility of Paracetamol and improve its bioavailability.

MATERIALS AND METHODS:

Paracetamol, Mannitol, PEG 6000 and Tween 20 were purchased procured form SD Fine chemicals, Mumbai and used at it is. All other chemicals and reagents used were of analytical grade and used as it is.

Standard curve of paracetamol:

Standard curve of Paracetamol was plotted by dissolving 100mg of the drug in 100mL methanol. 1mL of the above solution was pipette out and transferred to a 100mL volumetric flask and the volume was made up to the mark with methanol. This solution served as the stock solution. From the stock solution 1, 2, 3, 4 and 5mL of solution were pipette out and transferred to 10mL volumetric flasks and the volume was made up to the mark with methanol. The dilutions were coded as A, B, C, D and E respectively.

The dilutions were analyzed for absorbance at 257nm using a UV-Visible spectrophotometer² (Shimadzu, Pharmaspec series, UV1700). The calibration curve was obtained in accordance with Beer-Lambert law. (Figure 1)

Phase solubility studies:

Phase solubility studies on pure drug and with different carriers like PEG 6000, Tween 20 and mannitol were performed by the method described by Higuchi and Connors³. Excess amount of drug (10 mg) was added to 25 ml of distilled water containing various concentrations of carriers (0, 0.25, 0.5, 0.75, 1.0 and 1.25% w/v). The suspensions were shaken for 3 hours on a rotary flask shaker at 37 ± 1ºC and filtered through Whatman no.1 filter paper. The filtrates so obtained were analyzed spectrophotometrically at 257 nm and corresponding concentrations of the drug were computed from the standard curve. (Table 1)

RESULTS AND DISCUSSIONS:

Aqueous solubility of drug plays an important role in the dissolution of drug in the gastrointestinal tract. Drugs with poor aqueous solubility exhibit poor bioavailability and may also undergo opsonization. This leads to loss of therapeutic efficacy of the drug molecule and also causes an increase in dose of the drug. This can be overcome by increasing the aqueous solubility by different approaches and one such approach is the use of carriers as solubilizing agents.

The results of phase solubility studies for the Paracetamol and PEG 6000, Tween 20 and mannitol are shown in table and depicted graphically in the Figure 2. The solubilizing ability of the various carriers was found to be in the following order: PEG 6000 > Tween 20 > mannitol. In all cases solubility of Paracetamol increased linearly as a function of carrier concentration and the solubility curve can be classified as Higuchi’s type A_L. Because the straight line had a slope less than unity the increase in solubility was due to the formation of 1:1 complex. The apparent stability constant (Kc)⁴ obtained from the slope of the linear portion of the phase solubility diagram was found to be 85mg^-1, 60.3mg ^-1, and 31mg^-1 respectively with PEG 6000, Tween 20 and mannitol.

Figure 1: Standard curve of paracetamol

Figure 2: Effect of carrier on solubility of paracetamol

Table 1: Effect of carriers on the solubility of paracetamol

S. No.	Carrier concentration (%w/w)	Solubility of Paracetamol (µg/mL)
		Mannitol	Tween 20	PEG 6000
1	0.0	17.0	17.0	17.0
2	0.25	18.0	18.5	20.5
3	0.50	19.3	21.0	24.0
4	0.75	21.0	23.0	28.0
5	1.0	21.5	25.5	31.5
6	1.25	24.0	27.0	35.0

REFERENCES:

1. Burke A, Symth EM and Fitzgerald GA. Analgesic-Antipyretic agents; Pharmacotherapy of Gout. In Goodman and Gilman’s The Pharmacological Basis of Therapeutics Edited by Brunton LL, Laso JS and Parker K. McGraw-Hill, New York. 2006; 11^th ed: pp. 671-.

2. Indian Pharmacopoeia, Vol. 2, 1996, Controller of Publications, Ministry of Health and Family Welfare, Govt. of India, 554.

3. Higuchi T and Connors KA. Phase solubility techniques. Adv Anal Chem Instr. 1965; 4: 117-212.

4. Rukmani, K. et al., Indian drugs, 36(1), 1999, 66.

Received on 23.11.2008 Modified on 25.02.2009

Research J. Pharm. and Tech.2(2): April.-June.2009,;Page 419-420