Comprehensive evaluation of extemporaneous preparation containing ambroxol HCl and salbutamol sulfate: Compatibility, chemometrics, and stability study

Michael Raharja Gani Jeffry Tanriono Florentinus Dika Octa Riswanto Dina Christin Ayuning Putri Dita Maria Virginia Sri Hartati Yuliani   

Open Access   

Published:  Jun 12, 2022

DOI: 10.7324/JAPS.2022.120912

Extemporaneous compounding preparations of divided powder were commonly prescribed in Indonesia. Since it is important to implement the Good Pharmacy Practices Guideline, the compounded preparations should be evaluated for several quality parameters. This study aimed to perform a comprehensive evaluation of extemporaneous compounding preparation containing ambroxol HCl and salbutamol sulfate, including compatibility, chemometrics, and stability study. A compatibility study was carried out by evaluating FTIR spectroscopy on functional group change during the interaction between drugs and excipients. A chemometric approach of multivariate calibration was conducted to build predictive content determination for ambroxol HCl and salbutamol sulfate. It was found that the selected models for ambroxol HCl and salbutamol sulfate were partial least squares (PLS) on second derivative spectra and PLS on Savitzky–Golay spectra, respectively. The equation of multivariate calibration for ambroxol HCl was y = 0.975x−0.089 (Rval 2 = 0. 989), whereas the equation of multivariate calibration for salbutamol sulfate was y = 0.970x−0.119 (Rval 2 = 0.943). These models were employed for content determination in the stability study. Divided powder preparation samples were stable during seven days of storage.

Keyword:     Ambroxol HCl compatibility multivariate calibration salbutamol sulfate stability


Gani MR, Tanriono J, Riswanto FDO, Putri DCA, Virginia DM, Yuliani SH. Comprehensive evaluation of extemporaneous preparation containing ambroxol HCl and salbutamol sulfate: Compatibility, chemometrics, and stability study. J Appl Pharm Sci, 2022. doi:

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abdul-jabbar S, Wong DW, Martin GP, Woodhead B, Royall PG. Repurposing melt degradation for the evaluation of mixed amorphouscrystalline blends. AAPS Pharm Sci Tech, 2021; 22(105):1-6.

Aminu N, Chan S-Y, Mumuni MA, Umar NM, Tanko N, Zauro SA, Aminu A, Toh S-M. Physicochemical compatibility studies of triclosan and flurbiprofen with excipients of pharmaceutical formulation using binary, ternary, and multi-combination approach. Futur J Pharm Sci, 2021; 7(1):1-16.

Bajaj S, Sakhuja N, Singla D. Stability Testing of Pharmaceutical Products. J Appl Pharm Sci, 2012; 2012(03):129-38.

Biancolillo A, Marini F. Chemometric methods for spectroscopybased pharmaceutical analysis. Front Chem, 2018; 6:576.

Chakraborty S, Sharmin S, Rony SR, Ahmad SAI, Sohrab MDH. Stability-indicating UV/Vis spectrophotometric method for diazepam development and validation. Indian J Pharm Sci, 2018; 80(2):366-73.

Daharwal SJ, Jangade RK, Thakur VD, Sahu BP. Compatibility study of ambroxol HCl drug-excipients by using IR spectroscopy. Res Artic, 2013; 3(3):98-101.

Darji MA, Lalge RM, Marathe SP, Mulay TD, Fatima T, Alshammari A, Lee HK, Repka MA, Narasimha Murthy S. Excipient stability in oral solid dosage forms: a review. AAPS PharmSciTech, 2018; 19(1):12-26.

Dave V, Haware R, Sangave N, Sayles M, Popielarczyk M. Drug-excipient compatibility studies in formulation development: current trends and techniques. American Association of Pharmaceutical Scientists (AAPS) Formulation Design and Development (FDD) Section Newsletter, 9-15, 2015.

Dijkers E, Nanhekhan V, Thorissen A, Marro D, Uriel M. Limited influence of excipients in extemporaneous compounded suspensions. Hosp Pharm, 2017; 52(6):428.

Goyal RN, Oyama M, Singh SP. Fast determination of salbutamol, abused by athletes for doping, in pharmaceuticals and human biological fluids by square wave voltammetry. J Electroanal Chem, 2007; 611(1-2):140-8.

International Pharmaceutical Federation. Pharmacists' role in "Medication without harm" [Internet]. International Pharmaceutical Federation, Hague, The Nrtherlands, pp 1-105, 2020.

Jeli? D, Papovi? S, Vraneš M, Gadžuri? S, Berto S, Alladio E, Gaji? D, Jankovi? B. Thermo-analytical and compatibility study with mechanistic explanation of degradation kinetics of ambroxol hydrochloride tablets under non-isothermal conditions. Pharmaceutics, 2021; 13(11):1-29.

Jeli?i? ML, Brusa? E, Kurajica S, Cvetni? M, Klari? DA, Nigovi? B, Mornar A. Drug-drug compatibility evaluation of sulfasalazine and folic acid for fixed-dose combination development using various analytical tools. Pharmaceutics, 2021; 13(3):400.

Kantar A, Klimek L, Cazan D, Sperl A, Sent U, Mesquita M. An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children. Multidiscip Respir Med, 2020; 15(1):511.

Levent A, Yardim Y, Sentürk Z. Electrochemical performance of boron-doped diamond electrode insurfactant-containing media for ambroxol determination. Sens Actuators B Chem, 2014; 203:517-26.

Ministry of Health, The Republic of Indonesia and Indonesia Pharmacists Association. Good Pharmacy Practice, Jakarta, Indonesia, 2011.

Mevik B, Wehrens R. Introduction to the pls Package. R Package Notes. 2019. Mohiuddin A. Extemporaneous compounding: cautions, controversies and convenience. Innov J Med Heal Sci, 2019; 9(1):252-64.

Mohiuddin A. Extemporaneous compounding: selective pharmacists with separate skill. Inov Pharm, 2019; 10(4):3.

Murthy SN, Repka MA. Excipient stability: a critical aspect in stability of pharmaceuticals. AAPS PharmSciTech, 2018; 19(1):11.

Putri DCA, Gani MR, Riswanto FDO. Chemometrics-assisted UV spectrophotometric method for simultaneous determination of paracetamol and tramadol in divided powder dosage form. Int J Pharm Res, 2020; 13(01).

Riswanto FDO, Rohman A, Pramono S, Martono S. The employment of UV-Vis spectroscopy and chemometrics techniques for analyzing the combination of genistein and curcumin. J Appl Pharm Sci, 2021; 11(3):154-61.

Rohman A, Dzulfianto A, Riswanto FDO. The employment of UV-spectroscopy combined with multivariate calibration for analysis of paracetamol, propyphenazone and caffeine. Indones J Pharm, 2017; 28(4):191.

Rojek B, Wesolowski M. FTIR and TG analyses coupled with factor analysis in a compatibility study of acetazolamide with excipients. Spectrochim Acta Part A Mol Biomol Spectrosc, 2019; 208:285-93.

Seçilmi? Canbay H, Polat M, Do?antürk M. Study of stability and drug-excipient compatibility of estriol. Bilge Int J Sci Technol Res, 2019; 3:102-7.

Sharma D, Singh G, Kumar D, Singh M. Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate, cetirizine hydrochloride in combined pharmaceutical dosage form: a new era in novel drug delivery for pediatrics and geriatrics. J Drug Deliv, 2015; 2015:1-10.

Sharma D, Singh R, Singh G. Orally-disintegrating tablets in fixed-dose combination containing ambroxol hydrochloride and salbutamol sulphate prepared by direct compression: Formulation design, development and in vitro evaluation. Turkish J Pharm Sci, 2018; 15(1):29-37.

Singh I, Juneja P, Kaur B, Kumar P. Pharmaceutical applications of chemometric techniques. ISRN Anal Chem, 2013; 2013:1-13.

Swathi R, Reddy MS. UV-visible spectrometric method and validation, compatibility studies of nevirapine cubosome formulation. World J Pharm Pharm Sci, 2016; 6(01):1111-21.

Tamura K, Ono M, Kawabe T, Yonemochi E. Impact of magnesium stearate content: modeling of drug degradation using a modified arrhenius equation. Chem Pharm Bull, 2020; 68(11):1049-54.

Thummala VRR, Ivaturi MR, Nittala SR. Isolation, identification, and characterization of one degradation product in ambroxol by HPLCHyphenated techniques. Sci Pharm, 2014; 82(2):247-63.

Virginia DM. The prescription of compounding preparations for pediatric patients in inpatient wards. J Penelit, 2014; 18(1):56-61.

Wang Y, Lu J, Li T, Zhou S, Wen Y, Liu L, Shi X, Ding L. Investigation of a potential drug-drug interaction between salbutamol and ambroxol and bioequivalence of a new fixed-dose combination containing these two drugs in healthy Chinese subjects. Int J Clin Pharmacol Ther, 2018; 56(5):247-54.

World Health Organization. WHO guidelines on Stability testing of active pharmaceutical ingredients and finished pharmaceutical products. WHO Technical Report Series 1010, annex 10, WHO, Geneva, Switzerland, 2018.

Winter S De, Vanbrabant P, Vi NTT, Deng X, Spriet I, Schepdael A Van, Gillet J-B. Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting. Ann Emerg Med, 2013; 62(4):380-7.e1.

Yarnykh TG, Kotvitska AA, Tykhonov AI, Rukhmakova OA. Pharmaceutical incompatibilities: causes, types and major ways of overcoming in extemporaneous medicinal forms. Res J Pharm Technol, 2020; 13(7):3459-65.

Yuliani SH, Putri DCA, Widayati A, Abiyoga B. Compounding practice in a developing country: a case study of divided powder in Indonesia. Res J Pharm Technol, 2020; 13(12):6231-7.

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