Density and Optical Properties of { Ciprofloxacin Hydrochloride + Aqueous-Ethanol } Mixtures at 30 ∘ C

The paper deals with the calculation of molar refraction (R M ) and polarizability (α) of antibiotic drug ciprofloxacin hydrochloride (c = 0.001–0.029mol⋅dm) solutions in ethanol-water mixtures of different compositions (30, 50, and 70% v/v) from measured density (ρ) and refractive index (n) at 30C.The effect of drug concentration and composition of ethanol-water mixtures on density and optical properties of drug solutions has been described.


Introduction
The knowledge of physiochemical properties of drug solution plays an important role in understanding their physiological actions which is highly dependent upon solution behaviour.Drugs are organic molecules with both hydrophilic and hydrophobic groups due to which they show specific as well as electrostatic interactions.Physiochemical properties like  and  of solution are directly related to interactions in solution and are useful for recognition of substance; they confirm purity and concentration of substance.Refractive index along with density is used for investigated intermolecular interactions in solution.Molecular interactions are studied through the measurements of refractive indices of solution [1][2][3]. and   are useful for getting the valuable information about polarizability of solution [4][5][6][7][8].
Ciprofloxacin is second-generation fluoroquinolone used as an antibiotic that can treat a number of bacterial infections.It is used to treat infections such as infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, and urinary tract infections.We have studied the optical properties of aqueous metoprolol succinate and duloxetine solutions [9,10] and ciprofloxacin + aqueous-glycine solutions [11].Here we report  and  of ciprofloxacin hydrochloride solutions in ethanol-water mixtures of 30, 50, and 70% v/v at 30 ∘ C.   and  of these solutions are calculated.Various properties are interpreted in terms of molecular interactions in solution.Present work deals with the molecular interactions and overall structural fitting in the drug in aqueous-ethanol solutions and therefore finds the applications in pharmaceutical and medical sciences.The data of thermodynamic properties is helpful for understanding the drug-water and drug-alcohol interactions.

Experimental
The ciprofloxacin hydrochloride monohydrate drug was received as a gift sample from Godavari Drugs Ltd., Nanded (MS), India.Ethanol-water mixtures of 30, 50, and 70% v/v were prepared and drug solutions of different concentrations were prepared in given ethanol-water mixtures.Distilled water was used for preparation of drug solutions.Weighing was done on single pan electronic balance (±0.001 g). were determined using calibrated single capillary pycnometer and  were measured on thermostatically controlled Cyber LAB-Cyber Abbe Refractometer (Amkette Analytics, ±0.0002, 1.3000 to 1.7000).Averages of three readings of  and  are reported.

Results and Discussion
Experimental , ,   , and  data of ternary {ciprofloxacin hydrochloride + ethanol-water} systems at 30 ∘ C are presented in Table 1. and  of solutions increased with drug concentration and  decreased and  increased with increase in vol % of ethanol in solution for given drug concentration (Figures 1 and 2).As drug concentration increases, due to the drug-solvent interactions, volume contraction occurs which resulted in increase in density of solution.The  and  changes are indicative of intermolecular interaction in solution.
Concentration dependence of  is studied [12] using (1) and respective graphical parameters are reported in Table 2: where  is constant which depends on chemical and physical properties of solute (dm 3 ⋅mol −1 ),  is molar concentration of drug solution (mol⋅dm −3 ), and  0 is refractive index at infinite dilution.Relationship between  and  is also studied (Figure 3) and found to be linear ( 2 > 0.950).
The parameters   and  in Table 1 are determined using the following equations [13][14][15] and presented in Figures 4  and 5:   where   is mole fractions of th component of mixture and   is molecular mass of -component of mixture and where  is Avogadro's constant (6.023 × 10 23 mol −1 ).  is an electronic polarizability per mole of component which includes contributions from each component.Deviation in   is an indication of interactions between components [16].It is used in QSAR studies for drug design [17].  and  appear as a response to combined effects of intermolecular forces between solute and its surroundings [18].Use of   and  has become increasingly important in the study of drug interaction.  increased slightly with drug concentration and largely with vol % of ethanol in solution which indicates strong drugsolvent interactions [19].Plots of   with concentration of drug for all the systems are found to be linear ( 2 > 0.995).  is directly proportional to  [20]; hence,  increases and becomes stronger with increase in amount of drug which elucidates structural cause of change in density and existence and modification of molecular interactions.Changes in   and   indicate tighter packing of drug  molecules and strengthening of drug-solvent interactions at higher concentration.With increase in vol % of ethanol, the packing of drug becomes tighter.
is related to the intermolecular forces in the system like drug-receptor interactions [16].It is increased with drug concentration as well as with vol % of ethanol in solution which indicates capability of electronic system of drug molecule to be distorted is increase with drug concentration and vol % of ethanol.Stronger polarizability is introduced to drug solution upon addition of drug in ethanol-water mixtures due to interactions between polar parts of the drug and solvent dipoles.Both   and  values of ciprofloxacin in ethanolwater are higher than in aqueous medium [11].

Conclusions
The  values of ciprofloxacin in aqueous-ethanol mixtures show linear dependence over drug concentration and density. increases and becomes stronger with increase in amount of drug due to structural cause of change in density and existence and modification of drug-solvent interactions.Overall results indicated the strengthening of drug-solvent interactions with drug concentration.Capability of electronic system of drug to be distorted is increased with drug concentration and vol % of ethanol.

Figure 1 :
Figure 1:  with concentration of drug in ethanol-water at 30 ∘ C.

Figure 2 :
Figure 2:  with concentration of drug in ethanol-water at 30 ∘ C.

Figure 4 :
Figure 4:   with concentration of drug in ethanol-water at 30 ∘ C.

Figure 5 :
Figure 5:  with drug concentration in ethanol-water at 30 ∘ C.

Table 2 :
Graphical parameters from concentration dependence of .