Ultrasonic velocity and viscosity studies of tramacip and parvodex in binary mixtures of alcohol + water

Indian Journal of Pure & Applied Physics Vol. 46, December 2008, pp. 839-843 Ultrasonic velocity and viscosity studies of tramacip and parvodex in binary mixtures of alcohol + water Poonam Sharma*, S Chauhan, M S Chauhan & V K Syal Department of Chemistry, Himachal Pradesh University, Shimla 171 005 *E-mail : drpoonamsharma@rediffmail.com Received 23 May 2008; accepted 10 October 2008 The viscosity and ultrasound velocity of narcotic analgesic drugs in aqueous mixtures of methanol, ethanol and 1- propanol have been studied.. Various acoustical parameters have been obtained which include viscous relaxation time (), free (MCE). The dependence of these properties on solvent composition is found to originate from hydrophobic hydration phenomenon. Keywords: Methanol, Ethanol, 1-Propanol, Drug, Density, Viscosity, Ultrasonic velocity 1 Introduction One of the precise features that confer the solution properties of drug molecules is the implication of hydrophobic and charge contributions. In water, however since the polar groups are hydrated, the intermolecular aggregation of drug molecules through their hydrophobic parts is expected to occur in a way analogous to miscillization, favouring their limited aqueous solubilization 1. However, this aggregating tendency is affected with the addition of the nonaqueous component. The physico-chemical properties of such species have been studied in aqueous mixtures of such non-aqueous solvents which have a strong bearing on the structure of the water. The present work is in continuation of our earlier studies 2,3 on drug solutions in aqueous mixtures of alcohols. The results of acoustical parameters give support to the contributions arising from the size of the hydrophobic 4 groups of the alcohols. 2 Experimental Details Parvodex (PD) containing dextropropoxyphene hydrochloride and tramacip (TM) containing trammadol hydrochloride are classified as narcoticanalgesic drugs which are centrally active analgesics 5 that are effective for the management of moderate to moderately severe pain. The drugs parvodex and tramacip were procured from (Jagsonpal Pharmaceuticals Ltd, Faridabad) and (CIPLA Ltd, Mumbai, Central Mumbai 400 008), respectively. These drugs were used as supplied. Alcohols (methanol, ethanol and 1-propanol) all AR grade were obtained from S D Fine Chemicals Ltd. However, EtOH was obtained from Bengal chemicals and pharmaceuticals Ltd) was dried overnight on 4A o molecular sieves and was purified as reported in literature 6,7. Doubly distilled water was used for ultrasonic velocity, viscosity and density measurements. For all the measurements of drugs, different alcohol + water mixtures were prepared by volume (V/V). All the measurements were carried out at 25 ± 0.01 C in a water thermostat by using ultrasonic interferometer operating at frequency 1 MHz, Ubbelhode viscometer and calibrated sealable pycnometer. The ultrasonic velocity, viscosity and density values for methanol, ethanol and propan-1-ol are in good agreement with the literature values 7,8. 3 Results and Discussion Viscosity is one of the important parameters which determine the behaviour of drugs in solution. Also there are certain acoustical parameters which depend on viscosity. Thus, by combining ultrasonic velocity with density and viscosity of the solution, certain derived parameters like viscous relaxation time (), free volume (V f ), internal pressure (π i ) and molar cohesive energy (MCE) have been calculated using formulae 7,9 given below and these values have also been reported in Tables 1 and 2. Viscous relaxation time () = 4/(3ρ U 2 ) Free volume (V f ) = 3 M U K '

840 INDIAN J PURE & APPL PHYS, VOL 46, DECEMBER 2008 Table 1(a) Viscosity (), viscous relaxation time (), free (MCE) for drug Tramacip in MeOH + H 2 O solvent system C 10 2 0.963 1.017 1.114 1.157 1.198 1.073 1.123 1.166 1.220 1.271 1.320 1.113 1.166 1.219 1.268 1.314 0.780 0.836 0.885 0.933 0.980 1.021 30% MeOH 57.6 60.1 62.6 65.1 67.6 70.1 0.758 0.707 0.661 0.620 0.584 0.551 50% MeOH 81.1 82.5 85.6 88.7 91.7 94.6 0.672 0.650 0.612 0.577 0.546 0.518 70% MeOH 97.5 101.2 105.1 109.0 112.8 116.6 Internal Pressure (π i ) = 0.746 0.699 0.656 0.617 0.583 0.552 90% MeOH 97.5 1.090 102.4 1.000 107.6 0.925 112.7 0.857 117.8 0.798 122.7 0.745 brt M K U 7 / 6 6.591 6.744 6.897 7.046 7.191 7.332 6.116 6.186 6.314 6.438 6.560 6.678 5.354 5.471 5.588 5.703 5.814 5.922 4.232 4.352 4.472 4.587 4.699 4.790 β 2/3 (lit atm mol 1 ) 1.55 1.59 1.63 1.66 1.70 1.73 1.73 1.77 1.74 1.78 1.82 1.85 1.89 1.92 1.66 1.75 Molar cohesive energy (MCE) = π i V m These acoustic parameters, when examined under different experimental conditions give support for the contribution from solute-solute, solvent-solvent and solute-solvent interactions for the overall solution behaviour of the solute. Viscous relaxation time is directly proportional to viscosity and inversely related to adiabatic compressibility of solution or solvent system. From the Tables 1 and 2(a-c), it is clear that viscous relaxation time increases with increase in concentration of drugs in all studied solvent systems. However, it is particularly interesting to note that an increase in viscosity is relatively more prominent in case of water 1-PrOH solvent system than water- MeOH and water-etoh systems indicating considerable amount of hydrophobic interaction of 1-PrOH. Table 1(b) Viscosity (), viscous relaxation time (), free (MCE) for drug Tramacip in EtOH + H 2 O solvent system 2.180 2.230 2.227 2.330 2.375 2.421 2.216 2.264 2.312 2.357 2.395 2.441 1.667 6 1.764 1.811 1.853 1.893 1.012 1.060 1.106 1.151 1.192 1.230 30% EtOH 144.5 0.230 146.3 0.208 148.5 0.202 150.7 0.197 152.9 0.192 155.0 0.187 50% EtOH 182.8 184.9 187.3 190.2 192.7 195.2 0.206 0.192 0.143 0.113 0.091 70% EtOH 162.6 0.349 165.6 0.337 169.1 0.325 172.4 0.313 175.8 0.302 179.0 0.292 90% EtOH 118.5 121.7 126.4 131.1 135.6 140.1 0.785 0.747 0.701 0.660 0.623 0.590 10.158 10.408 11.463 12.422 13.306 13.964 8.721 9.023 9.105 9.186 9.265 9.343 6.865 6.949 7.036 7.121 7.205 7.287 4.675 4.753 4.855 4.954 5.050 5.144 MCE 10 5 2.409 2.468 2.718 2.946 3.155 8 2.461 2.546 2.564 2.92 2.614 2.636 2.251 2.278 2.306 2.334 2.361 2.387 1.81 1.88 1.92 1.96 2.00 Table 1(c) Viscosity (), viscous relaxation time (), free (MCE) for drug tramacip in 1- PrOH + H 2 O solvent system 3.273 3.323 3.368 3.412 3.455 3.489 4.064 4.143 4.192 4.239 4.278 3.751 3.800 3.855 3.903 3.950 3.992 V f 10 3 30% 1-PrOH 236.7 0.104 237.8 0.102 239.5 0.100 241.3 0.098 243.0 0.097 244.6 0.095 50% 1-PrOH 341.0 341.6 343.0 344.4 345.8 347.1 0.083 0.082 0.081 0.080 0.078 70% 1-PrOH 352.9 0.104 353.6 0.103 355.3 0.101 356.9 0.099 358.6 0.098 360.2 0.097 π I 10 3 0.123 1.299 1.307 1.314 1.321 1.328 1.241 1.246 1.251 1.256 1.261 1.268 1.047 1.056 1.061 1.071 3.012 3.026 3.043 3.059 3.076 3.092 3.425 3.437 3.450 3.464 3.477 3.495 3.342 3.354 3.369 3.384 3.398 3.412 Contd

SHARMA et al.:ultrasonic VELOCITY AND VISCOSITY OF BINARY MIXTURES 841 Table 1(c) Viscosity (), viscous relaxation time (), free volume (V f ), internal pressure (π i ) and molar cohesive energy (MCE) for drug tramacip in 1- PrOH + H 2 O solvent system Contd Table 2(b) Contd 3.421 3.475 3.529 3.576 3.622 3.664 V f 10 3 90% 1-PrOH 361.0 0.133 362.0 0.130 364.2 0.128 366.2 0.126 368.2 0.125 370.2 0.123 π I 10 3 8.720 8.760 8.806 8.851 8.896 8.941 3.248 3.262 3.278 3.294 0 3.326 Table 2(a) Viscosity (), viscous relaxation time (), free (MCE) for drug parvodex in MeOH + H 2 O solvent system 0.963 1.032 1.090 1.143 1.203 1.258 1.073 1.133 1.196 1.252 1.311 1.366 1.116 1.176 1.231 1.278 1.331 0.780 0.842 0.900 0.950 1.010 1.060 30% MeOH 57.6 60.4 63.3 65.4 68.1 70.8 0.758 0.709 0.665 0.631 0.595 0.562 50% MeOH 81.1 84.0 87.8 91.2 93.7 97.6 0.672 0.626 0.585 0.548 0.521 0.486 70% MeOH 97.5 97.8 07.9 113.0 118.0 123.1 0.746 0.682 0.626 0.578 0.537 0.500 90% MeOH 97.5 1.09 103.1 0.98 108.7 0.90 114.5 0.82 120.0 0.76 125.3 0.70 6.59 6.73 6.88 7.00 7.14 7.28 6.11 6.26 6.40 6.55 6.66 6.82 5.35 5.51 5.67 5.83 5.98 6.12 4.23 4.37 4.51 4.64 4.77 4.89 1.55 1.59 1.65 1.69 1.72 1.75 1.83 1.91 1.74 1.79 1.89 1.94 1.99 1.67 1.72 1.77 1.82 Table 2(b) Viscosity (), viscous relaxation time (), free volume (V f ), internal pressure (π i ), molar cohesive energy (MCE) and apparent molar adiabatic compressibility (φ ks ) for drug parvodex in EtOH + H 2 O solvent system 2.180 2.254 2.314 2.367 2.430 2.480 30% EtOH 144.5 146.4 148.6 150.7 152.9 154.9 0.213 0.207 0.201 0.195 0.190 0.185 1.01 1.02 1.03 1.04 1.05 1.06 2.40 2.43 2.45 2.48 2.50 2.53 Contd 2.218 2.288 2.349 2.396 2.459 2.515 1.660 1.732 1.788 1.839 1.900 1.956 1.012 1.091 1.140 1.192 1.224 1.287 50% EtOH 182.8 184.9 187.5 190.0 192.4 194.7 0.206 0.200 0.194 0.188 0.183 0.178 70% EtOH 162.6 165.6 169.3 172.8 176.1 179.3 0.349 0.335 0.321 0.309 0.297 0.286 90% EtOH 11805 12203 127.4 132.4 137.3 142.0 0.785 0.739 0.688 0.642 0.602. 0.567 8.94 9.03 9.12 9.21 9.30 9.39 6.86 6.96 7.06 7.15 7.25 7.34 4.67 4.77 4.88 5.00 5.11 5.21 2.52 2.54 2.57 2.59 2.62 2.64 2.25 2.28 2.31 2.34 2.37 2.40 1.81 1.85 1.90 1.94 1.98 2.02 Table 2(c) Viscosity (), viscous relaxation time (), free (MCE) for drug parvodex in 1-PrOH + H 2 O solvent system 3.273 3.341 3.386 3.431 3.486 3.525 4.119 4.172 4.226 4.267 4.324 3.751 3.829 3.880 3.932 3.994 3.421 3.501 3.545 3.621 3.662 3.719 30% 1-PrOH 236.7 0.104 237.5 1.012 238.9 0.100 240.3 0.098 241.6 0.096 242.9 0.095 50% 1-PrOH 341.1 340.6 341.6 342.3 342.9 343.5 0.083 0.082 0.081 0.080 0.078 70%1-PrOH 352.6 0.104 352.8 0.103 352.0 0.012 354.7 0.099 355.6 0.098 356.4 0.097 90% 1-PrOH 361.0 361.3 362.7 364.1 365.3 366.5 1.32 1.30 1.28 1.26 1.24 1.23 1.293 1.300 1.308 1.315 1.323 1.330 1.241 1.246 1.251 1.256 1.261 1.266 1.047 1.054 1.061 1.071 0.8720 0.876 0.880 0.885 0.890 0.894 3.01 3.028 3.045 3.063 3.080 3.097 3.425 3.437 3.451 3.465 3.478 3.491 3.342 3.355 3.361 3.385 3.400 3.414 3.24 3.26 3.28 3.29 3.32

842 INDIAN J PURE & APPL PHYS, VOL 46, DECEMBER 2008 Free volume (V f ) is average volume in which the central molecule can move inside the hypothetical cell due to repulsion of surrounding molecules. It is also referred as the void space between the molecules i.e. volume present as holes of monomeric size, due to irregular packing of solvent molecules 10,11. From Tables 1 and 2(a-c) for studied drugs PD and TM, it can be seen that V f values in general decrease in magnitude with the increase of concentration of drug at all composition. However, with the increase of alcohol content in water-alcohol mixtures, V f increases. Further, for various alcohols, its value is maximum in MeOH and minimum in 1-PrOH. Figure 1 shows the variation of V f with the composition of EtOH for the drugs TM and PD at one fixed concentration 7.5 10 2 mol dm 3 where a minimum at 50% (V/V) of EtOH is observed indicating its dependence upon viscosity. As reported in our earlier studies, a maximum is obtained for viscosity at around 50% (V/V) in aqueous mixtures of MeOH, EtOH and 1-PrOH due to some kind of structural organization 12 of water surrounding the hydrocarbon chain of alcohol molecules. Since free volume is reciprocal to viscosity, thereby, showing a minima at the same position. The internal pressure (π i ) which is the resultant of forces of attraction and repulsion between solute and solvent molecules of the solution also increases with increase of drug concentration and decreases with increase of alcohol content in alcohol + water solvent systems. Further, a linear increase of π i with concentration C (Fig. 2) indicates increase in intermolecular interactions which may be due to the formation of aggregates 10,11 of solvent molecules around the drug, affecting the structural arrangement in the solvent system. However, π i for various alcohols follow the order: water-meoh < water-etoh < water-1-proh which is reverse order as found for V f. However, MCE connotes the free energy state of liquid system related top the escaping tendency, which is quintessential connotation due to the totality of the contributions of all its constituents-molecules in whatever state of aggregation, ions etc. Figure 3 shows the plot of molar cohesive energy (MCE) versus concentration for drug PD in various aqueous mixtures of EtOH, thereby, showing a linear increase with increase in concentration of drug, at each composition. Parsania and Sanaria 13 have also reported that MCE increase linearly with C for all concentrations for epoxy resins of 1,1 -bis(r,4- hydroxyphenyl) cyclohexane (R = H, CH 3 ) in chloroform and 1,4-dioxane at 30 C which has been accounted for the enhancement of the structure forming tendency of the solvent molecules. The variation of energy in different alcohols is as follows: water-meoh < water-etoh < water-1-proh which again is indicative of greater hydrophobic interactions due to larger alkyl group. Also, from Fig. 1 Free volume (V f ) versus %age composition of EtOH for drugs tramacip and parvodex at one fixed concentration i.e. 7.50 10 2 mol dm 3 in aqueous mixtures of EtOH Fig. 2 Internal pressure (π I ) versus concentration of drug TM in aqueous mixtures of MeOH

SHARMA et al.:ultrasonic VELOCITY AND VISCOSITY OF BINARY MIXTURES 843 support the existence of drug-solvent interactions 14. These physico-chemical/drug-solvent interactions manifest themselves in terms of enhanced solubility and/or dissolution of the drug, prevention of drug precipitation if administered in solution form, and reduction in drug activity 1. The results obtained from these studies can, thus, be helpful for pharmacological application of drugs. Fig. 3 Molar cohesive energy (MCE) versus concentration of drug PD in aqueous mixtures of EtOH Tables 1 and 2(a-c), a maximum in MCE is observed at 50% (V/V) alcohol which shows its dependence on the viscosity of the medium. Further, as these systems are characterized by hydrogen bonding, the solute-solvent interactions can be interpreted in terms of structural changes that arise due to hydrogen-bond interactions between various components of the solvent and solution systems and also associated with the different extent of hydrophobic hydration of alcohol molecules. The studied drugs behave as structure promoter 3 and enhance the presence of interactions in the aqueous alcohol system. Various acoustical parameters also References 1 Yagui C O R, Junior A P & Tavares L C, J Pharm Parmaceut SciIndian Chem Soc,8(2),(2005) 147. 2 Chauhan S, Syal V K, Chauhan M S & Sharma Poonam, J Mol Liquids, 136 (2007) 161. 3 Chauhan S, Syal V K, Chauhan M S & Sharma Poonam, J Acta Acustica united with Acustica, 93 (2007) 566. 4 Kislev M & Ivlev D, J Mol Liq, 110(2004) 193. 5 Ashotoshkar, Medicinal Chemistry, (1995), Wiley Eastern Ltd, New York 6 Chauhan M S, Kumar G, Kumar A, Sharma K & Chauhan S, Colloids & Surfaces, 180 (2001) 111. 7 Syal V K, Chauhan S, Thakur S & Sharma P, Int J ThermoPhysics, 26 (2005) 807. 8 Weast R C, CRC Handbook of Chemistry & Physics, (1988-89) 69 th Ed CRC Press Inc, Boca Ratan FL. 9 Godhani D R, Patel Y V & Parsania P H ; J Pure & Appl Ultrason, 23 (2001)58. 10 Kumar D S & Rao D K, Indian J Pure & Appl Phys, 45(2007)210.220 11 Syal V K, Chauhan S, Chauhan Anita & Sharma Poonam, J Polymer Materials, 22 (2005)323. 12 Franks F & Ives D J G, Quart Rev, 20 (1966). 13 Sanaria M R & Parsania P H, J Pure & Appl Ultrason, 22 (2000) 54. 14 Jahangirdar D V, Arbad B R, Wabejar A A, Lande M K & Shankarwar A G; J Pure & Appl Ultrasonics, 21 (1999) 108.