Int. J. Pharm. Investigation, 2019;9(4):174-179 International Journal of Pharmaceutical Investigation, Vol 9, Issue 4, Oct-Dec, 2019 174 Original Article Preparation, Solid-State Characterization, Phase Solubility and Dissolution Studies of Azithromycin/Hydroxypropyl-β- Cyclodextrin Host-Guest System Mihir Raval, Hina Bagada* Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, INDIA. ABSTRACT Objectives: Azithromycin has poor aqueous solubility and its dissolution is the rate-limiting step. Therefore the objective of this work to increase the solubility and dissolution of azithromycin. Hence aim of the study was to develop, characterize and evaluate dissolution properties of inclusion complexes of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD). Methods: Phase solubility was performed by Higuchi and Connors’s meth- od for determination of stoichiometry of AZM/ β-CD and AZM/ HP-β-CD inclusion complex. It again confrmed by Jobs plot. Inclusion complex of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by kneading method and solvent evaporation method in molar ratio of 1:1. The inclusion complex in solid state was characterized by FT-IR, DSC, HNMR, SEM. Results: AL type was found in the phase solubility diagram which indicated the development of the inclusion complex in 1:1 stoichiometry with HP-β-CD. The stability constant decrease with increasing temperature. All thermodynamic parameters for the inclusion complex were calculated from Van’t Hoff plots. The highest enhancement in dissolution and solubil- ity were observed in the inclusion complex developed with HPβ-CD using the kneading method. FT-IR spectra exhibited that the hydroxyl group of azithromycin was participate in inclusion process. DSC study supported amorphization of drug molecule and entrapment of drug in the HP-β-CD cavity. It further confrmed with nuclear magnetic resonance and scanning electron microscopy studies. Conclusion: The solubility was signifcantly improved by the inclusion complex with HP-β-CD (9 fold). The dissolution of azithromycin was improved with inclusion phenomena using kneading method. The result of studies showed the inclusion of Azithromycin mol- ecule inside HP-β-CD cavities. Key words: Azithromycin, Hydroxypropyl-β-cyclodextrin, Inclusion complex, Kneading method Correspondence Hina Bagada, Department of Pharmaceutical Sciences, Saurashtra University, Rajkot-360005, Gujarat, INDIA. Phone no: +91-9979664719 Email: bagadahina@gmail.com DOI: 10.5330/ijpi.2019.4.33 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. INTRODUCTION Azithromycin (AZM) is one of the best antibiotic related to semisyn- thetic macrolide class. Azithromycin has mainly prevented the growth of bacteria such as Mycobacterium avium, Streptococcus, Staphylococcus au- reus, Pneumonia, Mycoplasma pneumonia, Haemophilus infuenza etc. 1 Azithromycin was useful for various disorders like pulmonary disease, pneumonia, respiratory tract disorders, bronchiectasis and nontubercu- lous mycobacterial pulmonary diseases. 2,3 According to BCS classifca- tion, Azithromycin (AZM) can be classifed as a class II drug. It means that it is a poorly water-soluble drug. 4,5 Te Supramolecular chemistry is one of an important part of chemical analysis. Tese studies explained about intermolecular interactions. 6,7 One type of intermolecular interaction is due to the host-guest system. 8 Cyclodextrin is one of the best choices to form an inclusion complex with the most lipophilic part of the molecule into the cavity. 9,10 Te inclusion complexes improve water solubility as well as stability. 11,12 Hence, this in- clusion complex has also modifed the physical as well as biological prop- erties of guest drug molecules. 13 Te interaction forces in the inclusion complex are the liberation of water molecules from the hydrophilic part, van der Waals interactions, electrostatic interactions, hydrogen bonding and hydrophobic interactions. Hydroxypropyl-beta-cyclodextrin (HP β-CD) and Beta-cyclodextrin were selected for this study to improve the dissolution rate of Azithromycin in phosphate bufer pH 6.8. Hence, the objective of this research work was to develop an inclusion complex of AZM with cyclodextrin in order to improve its dissolution. MATERIALS AND METHODS Material HP-β-CD and β-CD were obtained as gif sample from Roquette Rid- dhi Siddhi Pvt. Ltd. Mumbai India. Azithromycin dihydrate was also re- ceived as a gif sample from Alembic Pharmaceutical, Vadodara, India. All solvent and other chemicals used were A.R. grade. Double distilled water (fresh) was used during the work. Phase solubility Higuchi and Connors’s method was used for determination of phase-sol- ubility studies in triplicate. 14 Te phase solubility studies were performed with both cyclodextrin β-CD and HPβ-CD to evaluate the solubility. 25 ml of an aqueous solution of β-CD and HPβ-CD were prepared in screw- capped vials with increasing molar concentrations (0, 3, 6, 9, 12 and 15mM) at 25°C. Ten AZM, in constant amounts, was added to above solutions and stirred using rotary shaker (Remi, India) for 48 hr. For determination of Gibbs free energy of transfer (ΔG°), HPβ-CD molar concentration with AZM was stirred on a rotary shaker for 48 h at 25, 27, 33, 43°C on 300 rpm. 15 Te stirring time was decided on preliminary work to achieve equilibrium. Afer it, the mixture solution was fltered, diluted suitably and analyzed its AZM content at 510nm (UV/Visible spectrophotometer, Shimadzu). Te apparent stability constant (K1:1) for both AZM/ β-CD and AZM/HPβ-CD was calculated from the linear regression of the curve respectively.