The Physico-Chemical and Solvolytic Study of Alprazolam Drug In Ethanol at 303 K

Introduction

Alprazolam is a triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia and in generalized anxiety disorders.It is marketed under the trade name xanax.

 In the present study, we are reported the ultrasound velocity, density and viscosity measurements at 303K have been used to calculate Intermolecular freelength(L_f) [1] , Specific acoustic impedance(z) [2], Apparent molal adiabatic compressibility  (f_k  ) [3] ,  Shear’s  relaxation ( t_s ), and Solvation number (Sn) [4] of Alprazolam compound in ethanol at 303 K .  Several investigators have reported the results on ultrasound studies of liquid mixtures [4-12].

EXPERIMENTAL

The solutions were prepared by dissolving the accurately known weight of  Alprazolam in ethanol and kept for some time. A continuous interferometer technique was employed for measurement of ultrasound velocity at 2Mhz. The density and viscosity were determined using vibrating densitometer DMA 48  fitted with a Hook G thermostat and viscometer. The  experiment were reported atleast twice and results were reproducible with experimental error 0.00002 Kgm³ and 0.001 cm/ sec respectively.

Computation of different physical parameters

Ultrasound Velocity (V)

V = 2d × 10⁵ cm/ sec. or V = 2d × 10³ m/ sec

Density

where ‘M’: is the weight of the liquid filled in pyknometer used.

‘r’is radius of capillaries

‘h₁’& ‘h₂’are the heights of the liquid in capillaries

Viscosity ( η)

where

‘h’            is the viscosity of liquid

‘r’            is the density of liquid.

‘t’             is the time flow of liquid

‘a’&’b’     are viscometeric constants.

Specific Acoustic Impedance

Z = Vr.

Where, V and ‘p’ are the ultrasonic velocity and density respectively.

Isentropic Compressibility 

where ‘V’ is the ultrasound velocity and ‘p’ is the density of liquid mixtures.

Intermolecular Free Length

where,

‘K’ is temperature dependent constant.

Molal Adiabatic Compressibility

 

where ‘p⁰’ and ‘β_s⁰’ are compressibility and density of pure solvent and ‘β_s’ & ‘p’ are the compressibility and density of the solution respectively.

‘C’ is the concentration in mole/liter of solute.

‘M’ is the molecular weight of solute.

Solvation Number 

Where ‘ n₁ ‘ moles of solvent and ‘ n₂ ‘   moles of solute

Shear’s Relaxation Time (t)

RESULT AND DISCUSSION

The ultrasound velocity of the solution of Alprazolam drug in ethanol increases with increasing concentration Alprazolam drug which is shown in above table.

Table-: Alpra zolam + ethanol At 303K

Conc. of ethanol mol/litre	Ultrasound velocity m/sec.	Density gm/mol. (Exp.)	Specific Acoustic Impedance (C.G.S.) z´10-5	Isentropic compressibility (Exp.) cm2/dyne.1012	Lowering Isentropic compressibility cm2/deyne.1012	Intermolecular free length (Ao)	Viscosity (Exp.) (C.P.)	Apparent molal Adiabatic compressibility cm2/dyne.109	Solvation number	Shear’s Relaxation time
0.0025	1166	0.7883	0.0919	93.31	-6.76	0.6095	1.2546	-274.1037	46.2196	156.0890
0.0050	1170	0.7923	0.0927	92.20	-7.87	0.6059	1.2960	-167.4630	53.8089	159.3216
0.0075	1175	0.7965	0.0936	90.94	-9.13	0.6017	1.3374	-134.2552	62.4238	162.1642
0.0100	1178	0.8010	0.0944	89.97	-10.10	0.5985	1.3786	-115.1329	69.0559	165.3769
0.0125	1184	0.8052	0.0953	88.59	-11.48	0.5939	1.4201	-106.6343	78.4912	167.7422
0.0150	1188	0.8091	0.0961	87.57	-12.50	0.5905	1.4515	-98.3142	85.4652	169.4771
0.0175	1190	0.8137	0.0968	86.78	-13.29	0.5878	1.5026	-91.5657	90.8666	173.8608
0.0200	1196	0.8178	0.0978	85.49	-14.59	0.5834	1.5442	-88.7363	99.6866	176.0182
0.0225	1199	0.8199	0.0983	84.84	-15.23	0.5812	1.5853	-82.4719	104.1308	179.3291
0.0250	1202	0.8263	0.0993	83.76	-16.31	0.5775	1.6271	-81.4079	111.5150	181.7145

 

The variation of velocity with concentration ( C) can be expressed  by the following relationship.

The result shows that while the density increases, the isentropic compressibility decreases with increasing concentration of the solute and quantity (dp/dc) is positive while (dβ_s/ dc) is negative. Since the value of

are larger than the value of

for the system . The concentration derivatives of velocity( dv/dc) is positive. i.e. the ultrasonic velocity increases with increasing the concentration of solute (13-16).

Figure 1. A Click here to View Figure

 

Intermolecular free length and isentropic compressibility (  β_s  ) of Alprazolam drug solution decreases with increase in molar concentration of solute (Fig.1-b) .The complementary use of isentropic compressibility data can provide interesting information of of solute- solvent interaction.

Figure 1. B Click here to View Figure

 

Apparent molal adiabatic compressibility () varies linearly s the square root of concentration.The value of apparent molal adiabatic compressibilities are negative with the increase in molar concentration. The values of apparent molal adiabatic compressibility as shown in figure  1 (c) . The values of  for the solutions of Alprazolam drug  were tabulated in table. These results are in agreement with the result reported by Masson (17) for electrolytic solution.

Figure 1. C Click here to View Figure

 

The value of specific acoustic impedance (z) increases with increasing the concentration of Alprazolam drug can be explained on the basis of lyophobic interaction between solute and solvent molecules which increase the intermolecular distance making relatively under gaps between the molecules and becoming the main cause of impedance in the propagation of ultrasound waves are tabulated.

The increase with the concentration suggest a significant interaction between the solute solvent molecules and the values are in agreement with the reported for solution of cobalt carboxylates (18).

From the above discussion it is concluded that solvolytic study of Alprazolam in ethanol at 303 K shows specific ion – solvent interaction. Alprazolam drug shows significant solvolysis in ethanol.

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