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Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl

Yıl 2022, Cilt: 26 Sayı: 5, 1403 - 1410, 28.06.2025

Sri Hartati Yuliani Clara Angelika Sinulingga Dina Christin Ayuning Putri Michael Raharja Gani Florentinus Dika Octa Riswanto Dita Maria Virginia

Öz

Split powder preparations containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl were
frequently dispensed at a private hospital in Semarang, Central Java, Indonesia. Triprolidine HCl was reported to have a
low composition in the divided powder. Content uniformity is one of the most important characteristics of
extemporaneous formulations, especially for low-dose active ingredients. The aim of this study was to evaluate the dose
uniformity of the divided powder preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl
prepared by a pharmacist in a private hospital in Semarang, Central Java, Indonesia. In this study, the
spectrophotometric method was used in combination with the chemometric analysis to determine the drug
concentration in the divided powder. The accuracy of the models was evaluated by the highest value of the coefficient of
determination of calibration, cross-validation and validation, while the precision of the models was evaluated by the
lowest value of the mean square error of calibration, cross-validation and prediction. The selected model for each
compound was used to build predictive models for quantitative analysis. It was found that the content of ambroxol HCl,
pseudoephedrine HCl, and triprolidine HCl in the subdivided powder samples were 8.120 ± 1.167 mg, 30.142 ± 3.965 mg,
and 1.193 ± 0.221 mg, respectively. The results on the uniformity of the content did not meet the requirements, as it was
found that the coefficient of variance of these determinations was more than 5%. Surprisingly, the divided powder can
be considered as a safe and acceptable dosage form due to its wide therapeutic window.

Anahtar Kelimeler

Ambroxol HCl pseudoephedrine HCl triprolidine HCl divided powder quality

Kaynakça

  • [1] Yuliani SH, Putri DCA, Virginia DM, Kajian Risiko Peracikan Obat,first ed., Sanata Dharma University Press, Yogyakarta, Indonesia 2020.
  • [2] Villegas SC. Prescribing oral liquid formulations for pediatric patients. J Develop Drugs. 2013; 2(3): 6631.
  • [3] Muśko M, Sznitowska M. Stability of extemporaneous pediatric oral liquids compounded from tablets and drug substance: case of propranolol and theophylline. Acta Pol Pharm. 2013; 70(1): 137–145.
  • [4] Sellers S, Utian WH. Pharmacy Compounding Primer for Physicians Prescriber Beware. Drugs. 2012; 72(16): 2043– 2050. [CrossRef]
  • [5] Riswanto FDO, Virginia DM, Putri DCA, Yuliani SH. Analytical method validation and determination of dexamethasone in divided powder using reverse phase HPLC. Pharmaciana. 2017; 7(2): 169-176. [CrossRef]
  • [6] Naveed S, Akhtar F, Khan S. An overview on stability of extemporaneously prepared pharmaceutical suspension. J Bioequiv Availab. 2017; 9(4): 452–454. [CrossRef]
  • [7] Jackson M, Lowey A, Handbook of Extemporaneous Preparation A Guide to Pharmaceutical Compounding, Pharmaceutical Press, London, Chicago 2010.
  • [8] Lowey A, Jackson M. How to ensure the quality and safety of unlicensed oral medicines. Pharm J. 2008; 281(7517): 240–243.
  • [9] Yuliani SH, Putri DCA, Widayati A, Abiyoga B. Compounding practice in a developing country: a case study of divided powder in Indonesia. J Res Pharm Technol. 2020; 13(12): 6231-6237. [CrossRef]
  • [10] Narang AS, Desai D, Badawy S. Impact of excipient interactions on solid dosage form stability. Pharm Res. 2012; 29: 2660–2683. [CrossRef]
  • [11] Panakanti R, Narang AS. Impact of excipient interactions on drug bioavailability from solid dosage forms. Pharm Res. 2012; 29: 2639–2659. [CrossRef]
  • [12] Kardos P, Beeh KM, Sent U, Mueck T, Gräter H, Michel MC. Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations. BMC Pharmacol Toxicol. 2018; 19: 1– 11. [CrossRef]
  • [13] KantarA, 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. [CrossRef]
  • [14] Gelotte CK, Albrecht HH, Hynson J, Gallagher V. A multicenter, randomized, placebo-controlled study of pseudoephedrine for the temporary relief of nasal congestion in children with the common cold. J Clin Pharmacol. 2019; 59(12): 1573–1583. [CrossRef]
  • [15] Głowacka K, Wiela-Hojeńska A. Pseudoephedrine—benefits and risks. Int J Mol Sci. 2021; 22(10): 1-11. [CrossRef]
  • [16] National Institute of Diabetes and Digestive and Kidney Diseases Triprolidine. LiverTox Clin. Res. Inf. Drug- Induced Liver Inj. 2017, https://www.ncbi.nlm.nih.gov/books/NBK548164/#Triprolidine.OVERVIEW (accessed 3 February 2022).
  • [17] Febbraro S, Shea T, Cravo AS. Bioavailability of triprolidine as a single agent or in combination with pseudoephedrine: a randomized, open-label crossover study in healthy volunteers. Clin Pharmacol Drug Dev. 2020; 9: 486–495. [CrossRef]
  • [18] Joseph MM, King WD. Dystonic reaction following recommended use of a cold syrup. Ann Emerg Med. 1995; 26(6): 749–751. [CrossRef]
  • [19] Boland DM, Rein J, Lew EO, Hearn WL. Fatal cold medication intoxication in an infant. J Anal Toxicol. 2003; 27(7): 523–526. [CrossRef]
  • [20] Isbister GK, Prior F, Kilham, HA. Restricting cough and cold medicines in children. J Paediatr Child Health. 2012; 48(2): 91–98. [CrossRef]
  • [21] Sosnowska K, Winnicka K, Czajkowska-Kośnik, A. Stability of extemporaneous enalapril maleate suspensions for pediatric use prepared from commercially available tablets. Acta Pol Pharm. 2009, 66(3): 321–326.
  • [22] Singh I, Juneja P, Kaur B, Kumar, P. Pharmaceutical applications of chemometric techniques. ISRN Anal Chem. 2013; 2013: 1–13. [CrossRef]
  • [23] Biancolillo A, Marini F. Chemometric methods for spectroscopy-based pharmaceutical analysis. Front Chem. 2018; 6:1-14. [CrossRef]
  • [24] 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. 2021; 13(1): 1901- 1907. [CrossRef]
  • [25] Rohman A, Dzulfıanto A, Rıswanto FDO. The employment of UV-spectroscopy combined with multivariate calibration for analysis of paracetamol, propyphenazone and caffeine. Indones J Pharm. 2017; 28(4):191-197. [CrossRef]
  • [26] Riswanto FDO, Lukitaningsih E, Martono S. Analytical method validation and determination of pyridoxine, nicotinamide, and caffeine in energy drinks using thin layer chromatography-densitometry. Indones J Chem. 2015; 15(1): 9-15
  • [27] Gani MR, Riswanto FDO. Ultraviolet spectroscopy combined with multivariate calibration for analysing caffeine, nicotinamide and pyridoxine in simulated energy drinks. Int J Pharm Res. 2021; 13(1): 579-587. [CrossRef]
  • [28] Kassambara A, Machine Learning Essentials: Practical Guide in R, STHDA, 2018.
  • [29] Nguyen KQ, Hawkins MG, Taylor IT, Wiebe VJ, Tell LA. Stability and uniformity of extemporaneous preparations of voriconazole in two liquid suspension vehicles at two storage temperatures. Am J Vet Res. 2009; 70: 908–914. [CrossRef]
  • [30] MIMS, 2021. Ambroxol. Generic Medicine Info. Monthly Index of Medical Specialities, https://www.mims.com/indonesia/drug/info/ambroxol?mtype=generic (accessed on 3 February 2022).

Yıl 2022, Cilt: 26 Sayı: 5, 1403 - 1410, 28.06.2025

Sri Hartati Yuliani Clara Angelika Sinulingga Dina Christin Ayuning Putri Michael Raharja Gani Florentinus Dika Octa Riswanto Dita Maria Virginia

Öz

Kaynakça

  • [1] Yuliani SH, Putri DCA, Virginia DM, Kajian Risiko Peracikan Obat,first ed., Sanata Dharma University Press, Yogyakarta, Indonesia 2020.
  • [2] Villegas SC. Prescribing oral liquid formulations for pediatric patients. J Develop Drugs. 2013; 2(3): 6631.
  • [3] Muśko M, Sznitowska M. Stability of extemporaneous pediatric oral liquids compounded from tablets and drug substance: case of propranolol and theophylline. Acta Pol Pharm. 2013; 70(1): 137–145.
  • [4] Sellers S, Utian WH. Pharmacy Compounding Primer for Physicians Prescriber Beware. Drugs. 2012; 72(16): 2043– 2050. [CrossRef]
  • [5] Riswanto FDO, Virginia DM, Putri DCA, Yuliani SH. Analytical method validation and determination of dexamethasone in divided powder using reverse phase HPLC. Pharmaciana. 2017; 7(2): 169-176. [CrossRef]
  • [6] Naveed S, Akhtar F, Khan S. An overview on stability of extemporaneously prepared pharmaceutical suspension. J Bioequiv Availab. 2017; 9(4): 452–454. [CrossRef]
  • [7] Jackson M, Lowey A, Handbook of Extemporaneous Preparation A Guide to Pharmaceutical Compounding, Pharmaceutical Press, London, Chicago 2010.
  • [8] Lowey A, Jackson M. How to ensure the quality and safety of unlicensed oral medicines. Pharm J. 2008; 281(7517): 240–243.
  • [9] Yuliani SH, Putri DCA, Widayati A, Abiyoga B. Compounding practice in a developing country: a case study of divided powder in Indonesia. J Res Pharm Technol. 2020; 13(12): 6231-6237. [CrossRef]
  • [10] Narang AS, Desai D, Badawy S. Impact of excipient interactions on solid dosage form stability. Pharm Res. 2012; 29: 2660–2683. [CrossRef]
  • [11] Panakanti R, Narang AS. Impact of excipient interactions on drug bioavailability from solid dosage forms. Pharm Res. 2012; 29: 2639–2659. [CrossRef]
  • [12] Kardos P, Beeh KM, Sent U, Mueck T, Gräter H, Michel MC. Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations. BMC Pharmacol Toxicol. 2018; 19: 1– 11. [CrossRef]
  • [13] KantarA, 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. [CrossRef]
  • [14] Gelotte CK, Albrecht HH, Hynson J, Gallagher V. A multicenter, randomized, placebo-controlled study of pseudoephedrine for the temporary relief of nasal congestion in children with the common cold. J Clin Pharmacol. 2019; 59(12): 1573–1583. [CrossRef]
  • [15] Głowacka K, Wiela-Hojeńska A. Pseudoephedrine—benefits and risks. Int J Mol Sci. 2021; 22(10): 1-11. [CrossRef]
  • [16] National Institute of Diabetes and Digestive and Kidney Diseases Triprolidine. LiverTox Clin. Res. Inf. Drug- Induced Liver Inj. 2017, https://www.ncbi.nlm.nih.gov/books/NBK548164/#Triprolidine.OVERVIEW (accessed 3 February 2022).
  • [17] Febbraro S, Shea T, Cravo AS. Bioavailability of triprolidine as a single agent or in combination with pseudoephedrine: a randomized, open-label crossover study in healthy volunteers. Clin Pharmacol Drug Dev. 2020; 9: 486–495. [CrossRef]
  • [18] Joseph MM, King WD. Dystonic reaction following recommended use of a cold syrup. Ann Emerg Med. 1995; 26(6): 749–751. [CrossRef]
  • [19] Boland DM, Rein J, Lew EO, Hearn WL. Fatal cold medication intoxication in an infant. J Anal Toxicol. 2003; 27(7): 523–526. [CrossRef]
  • [20] Isbister GK, Prior F, Kilham, HA. Restricting cough and cold medicines in children. J Paediatr Child Health. 2012; 48(2): 91–98. [CrossRef]
  • [21] Sosnowska K, Winnicka K, Czajkowska-Kośnik, A. Stability of extemporaneous enalapril maleate suspensions for pediatric use prepared from commercially available tablets. Acta Pol Pharm. 2009, 66(3): 321–326.
  • [22] Singh I, Juneja P, Kaur B, Kumar, P. Pharmaceutical applications of chemometric techniques. ISRN Anal Chem. 2013; 2013: 1–13. [CrossRef]
  • [23] Biancolillo A, Marini F. Chemometric methods for spectroscopy-based pharmaceutical analysis. Front Chem. 2018; 6:1-14. [CrossRef]
  • [24] 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. 2021; 13(1): 1901- 1907. [CrossRef]
  • [25] Rohman A, Dzulfıanto A, Rıswanto FDO. The employment of UV-spectroscopy combined with multivariate calibration for analysis of paracetamol, propyphenazone and caffeine. Indones J Pharm. 2017; 28(4):191-197. [CrossRef]
  • [26] Riswanto FDO, Lukitaningsih E, Martono S. Analytical method validation and determination of pyridoxine, nicotinamide, and caffeine in energy drinks using thin layer chromatography-densitometry. Indones J Chem. 2015; 15(1): 9-15
  • [27] Gani MR, Riswanto FDO. Ultraviolet spectroscopy combined with multivariate calibration for analysing caffeine, nicotinamide and pyridoxine in simulated energy drinks. Int J Pharm Res. 2021; 13(1): 579-587. [CrossRef]
  • [28] Kassambara A, Machine Learning Essentials: Practical Guide in R, STHDA, 2018.
  • [29] Nguyen KQ, Hawkins MG, Taylor IT, Wiebe VJ, Tell LA. Stability and uniformity of extemporaneous preparations of voriconazole in two liquid suspension vehicles at two storage temperatures. Am J Vet Res. 2009; 70: 908–914. [CrossRef]
  • [30] MIMS, 2021. Ambroxol. Generic Medicine Info. Monthly Index of Medical Specialities, https://www.mims.com/indonesia/drug/info/ambroxol?mtype=generic (accessed on 3 February 2022).
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Farmakoloji ve Terapötikler
Bölüm Articles
Yazarlar

Sri Hartati Yuliani 0000-0001-5246-8252

Clara Angelika Sinulingga 0000-0002-2646-954X

Dina Christin Ayuning Putri 0000-0002-7722-7348

Michael Raharja Gani 0000-0002-4732-5457

Florentinus Dika Octa Riswanto 0000-0002-7174-6382

Dita Maria Virginia 0000-0003-0469-1913

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 5

Kaynak Göster

APA Yuliani, S. H., Sinulingga, C. A., Putri, D. C. A., Gani, M. R., vd. (2025). Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl. Journal of Research in Pharmacy, 26(5), 1403-1410.
AMA Yuliani SH, Sinulingga CA, Putri DCA, Gani MR, Riswanto FDO, Virginia DM. Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl. J. Res. Pharm. Haziran 2025;26(5):1403-1410.
Chicago Yuliani, Sri Hartati, Clara Angelika Sinulingga, Dina Christin Ayuning Putri, Michael Raharja Gani, Florentinus Dika Octa Riswanto, ve Dita Maria Virginia. “Chemometrics-Assisted Content Uniformity Evaluation of Extemporaneous Preparation Containing Ambroxol HCl, Pseudoephedrine HCl, and Triprolidine HCl”. Journal of Research in Pharmacy 26, sy. 5 (Haziran 2025): 1403-10.
EndNote Yuliani SH, Sinulingga CA, Putri DCA, Gani MR, Riswanto FDO, Virginia DM (01 Haziran 2025) Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl. Journal of Research in Pharmacy 26 5 1403–1410.
IEEE S. H. Yuliani, C. A. Sinulingga, D. C. A. Putri, M. R. Gani, F. D. O. Riswanto, ve D. M. Virginia, “Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl”, J. Res. Pharm., c. 26, sy. 5, ss. 1403–1410, 2025.
ISNAD Yuliani, Sri Hartati vd. “Chemometrics-Assisted Content Uniformity Evaluation of Extemporaneous Preparation Containing Ambroxol HCl, Pseudoephedrine HCl, and Triprolidine HCl”. Journal of Research in Pharmacy 26/5 (Haziran 2025), 1403-1410.
JAMA Yuliani SH, Sinulingga CA, Putri DCA, Gani MR, Riswanto FDO, Virginia DM. Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl. J. Res. Pharm. 2025;26:1403–1410.
MLA Yuliani, Sri Hartati vd. “Chemometrics-Assisted Content Uniformity Evaluation of Extemporaneous Preparation Containing Ambroxol HCl, Pseudoephedrine HCl, and Triprolidine HCl”. Journal of Research in Pharmacy, c. 26, sy. 5, 2025, ss. 1403-10.
Vancouver Yuliani SH, Sinulingga CA, Putri DCA, Gani MR, Riswanto FDO, Virginia DM. Chemometrics-assisted content uniformity evaluation of extemporaneous preparation containing ambroxol HCl, pseudoephedrine HCl, and triprolidine HCl. J. Res. Pharm. 2025;26(5):1403-10.