Defense

Partial Molar Volume of Some Antidepressant Drugs in Various Solvents at Different

Temperatures

Khurram Shahzad181

MPhil 3rd Semester

Supervised by

Dr. Muhammad Asghar Jamal

SummaryApparent molar volumes (V), partial molar volumes (Vo), partial molar expansivity (Eo), and partial molar compressibilities of four antidepressant drugs, Venlafaxine HCl, Escitalopram oxalate, Citalopram HBr, and Paroxetine HCl in water, ethanol, and aqueous CaCl2 will be calculated from precision densities and sound velocities by using density sound analyzer (DSA 5000) over temperature range (298.15 – 313.15) K in order to characterize the changes in the physico-chemical properties of these drugs. The results obtained will be discussed in terms of solute-solvent interactions. This study is a comprehensive investigation of the effect of solvents and temperature on volumetric properties and drug macromolecular interactions in biological systems

Need for the present work

• It is possible that accumulation of these anti-depressant drugs can occur at certain sites of the organism after medium to long periods of administration, giving rise to the formation of aggregates that are unable to pass through membranes, decreasing transport rates, and consequently leading to adverse effects on health.

• Scarcity of such work on antidepressant drugs

Significance of Present Work

• Interaction with biological membranes (Blood brain Barrier)

• Factors affecting the physical and biological properties of these drugs (Temperature, solvents and concentration of electrolyte)

• Study of self association (aggregate formation) of these drugs

Biological Membranes

Blood-Brain Barrier Pre-Synaptic Membrane

Review of Literature• Jamal and Iqbal (2011) calculated Apparent molar volume V), partial

molar volume (V0), solute-solute interaction parameter (Sv), partial molar expansivity (E0) and isobaric thermal expansion co-efficient () of twelve amino acids namely, alanine, arginine, asparagine, glutamic acid, glycine, histidine, leucine, lysine HCl, proline, serine, threonine and valine in water the measured solution densities over a temperature range of 283.15 to 313.15±0.01K. The behavior of these parameters has been used to investigate the solute-solute and solute-solvent interactions as well as the effect of temperature on these interactions.

• Iqbal and Mansoora (2009) measured the density and viscosity of Notriptyline HCl and Trimpramine HCl maleate and calculated partial molar volume, expansivity from the density data.

Review of Literature • Cheema et al (2006) investigated the Apparent molal volumes and

adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drugs butriptyline and doxepin hydrochlorides from density and ultrasound velocity measurements in the temperature range 20–50C. Critical concentrations for aggregation of these drugs were obtained from ultrasound velocity measurements.

• Gutierrez-Pichel‘ et al (2003) determined Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drugs imipramine and desipramine hydrochlorides from density and ultrasound velocity measurements in the temperature range 288.15313.15K in buffered solution of pH 3.0 and 5.5. Critical concentrations for aggregation of these drugs were obtained from inflections on the plots of the sound velocity against drug concentration.

Serotonin-Specific Reuptake Inhibitors (SSRIs)

• These are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders.

• SSRIs are believed to act by inhibiting the reuptake of serotonin after being released in synapses.

Serotonin-Specific Reuptake Inhibitors (SSRIs)

Escitalopram Oxalate

Citalopram

Venlafexine

Paroxetine

Serotonin

• Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter.

• It is a well-known contributor to feelings of well-being; therefore it is also known as a "happiness hormone" despite not being a hormone.

• It is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans

Serotonin

Mode of Action of SSRIs

Ca+2

Parameters

• Apparent Molal Volume (V) • Partial Molal Volume (Vo)• Partial Molal Expansivity (Eo)• Partial Molal Adiabatic Compressibilities• Critical Micellar Concentration

Target Investigations

• Solute-Solvent interactions• Solute-Solute interactions• Critical Micellar Concentrations

Feasibility

• Availability of Density Sound Analyzer (DSA 5000)

• Usage of Computational softwares• Availability of Pure salts

Present work can be Extended

• For studying the structural transformation of aggregates light scattering or NMR is required.

• Experimentation on Ternary and Quaternary systems

References• Cheema, M. A. , Taboada, P. , Barbosa, S. , Siddiq, M. and Mosquera, V.

(2006) 'Effect of molecular structure on the hydration of structurally related antidepressant drugs', Molecular Physics, 104: 20, 3203 — 3212

• GUTIÉRREZ-PICHEL, MANUEL , ATTWOOD, DAVID , TABOADA, PABLO and MOSQUERA, VÍCTOR. (2003) 'Influence of external factors on the self-assembly of two structurally related antidepressant drugs: a thermodynamic study', Molecular Physics, 101: 23, 3455 — 3465

• JAMAL, M. A. AND M. IQBAL (2011) ‘Volumetric Studies of Some Amino Acids in Aqueous Medium at Different Temperatures’ J.Chem.Soc.Pak., Vol. 33, No. 1, 71-74

• Iqbal, M. J., and M. A. Chaudaray, J. Chem. Eng. Data (2009)

Thank You!

Formulae

• V = (1000 / mdd0) (d0 - d) + (M / d)

• V = V0 + Svm

• E0 = [∂V0 / ∂T]p

• Ks = 106 / U2