Sri Hartati Yuliani, Dina Christin Ayuning Putri, Aris Widayati, Bagas Abiyoga
Sri Hartati Yuliani1*, Dina Christin Ayuning Putri1, Aris Widayati1, Bagas Abiyoga2
1Faculty of Pharmacy, Sanata Dharma University, Yogyakarta Special Region, Indonesia, 55281.
2Pharmacy Department, Bethesda Wonosari Hospital, Yogyakarta Special Region, Indonesia, 55851.
Volume - 13,
Issue - 12,
Year - 2020
Drug compounding is still carried out throughout the world, especially in developing countries like Indonesia. Drug compounding from the solid dosage formed by splitting or crushing the tablet might change the stability, pharmacokinetic profile, and drug irritation. Most of the pharmacist in Indonesia had a limited time to do a risk assessment for potential incompatibility and instability of drug combination in compounding preparation. This article was aimed to provide an overview of compounding practice in divided powder preparation in Indonesia and as a case study of potential incompatibility and instability of an extemporaneous preparation. This study is an observational study using a case study. The consideration in selecting the case is the prescription that is most frequently prescribed in five months of the study period will be chosen. Risk assessment of technical risk in compounding was conducted using a matrix based on the Handbook on Extemporaneous Preparation. Analysis of instability and incompatibility potency was conducted based on the literature review (descriptive analysis). There were 666 prescriptions that needed compounding preparation. The most frequently prescribed formula was the combination of cetirizine tablets, ketotifen tablets, and cyproheptadine tablets that must be crushed to be divided powder. The combination has instability potency. The instability might be prevented by proper packaging and storing. A pharmacist must be able to understand the physical and chemical properties of each drug that is prescribed to determine the potential instability and incompatibility that may occur in the compounding order. Furthermore, the pharmacist must decide the most appropriate solution to overcome the incompatibility or instability that occur. This is the part of quality assurance of compounding preparations, so that patients will get safe and effective drugs, and can prevent medication errors.
Cite this article:
Sri Hartati Yuliani, Dina Christin Ayuning Putri, Aris Widayati, Bagas Abiyoga. Compounding practice in a developing Country: A Case study of divided Powder in Indonesia. Research J. Pharm. and Tech. 2020; 13(12):6231-6237. doi: 10.5958/0974-360X.2020.01086.0
1. Kochanowska-Karamyan AJ. Pharmaceutical Compounding: The Oldest, Most Symbolic, and Still Vital Part of Pharmacy. Int J Pharm Compd. 2016;20(5): 367–374.
2. Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs RD. 2013;13(1): 1–8.
3. Aronson JK. Medication errors: what they are, how they happen, and how to avoid them. Qjm. 2009;102(8):513–521.
4. Monajjemzadeh F, Hassanzadeh D, Valizadeh H, et al. Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets. Eur J Pharm Biopharm. 2009;73(3): 404–413.
5. Byrn SR, Xu W, Newman AW. Chemical reactivity in solid-state pharmaceuticals: formulation implications. Adv Drug Deliv Rev. 2001;48(1): 115–136.
6. Pergolizzi Jr JV, Labhsetwar S, LeQuang JA. Compounding pharmacies: who is in charge? Pain Pract. 2013;13(3): 253–257.
7. Williams KG. Regulation of compounding by the Food and Drug Administration: a tale of 2 circuits. J Pharm Pract. 2010;23(5): 502–506.
8. Royal Pharmaceutical society. Pharmaceutical Issues when Crushing, Opening or Splitting Oral Dosage - Penelusuran Google. Royal Pharmaceutical society. https://www.google.com/search? client=firefox-b-d&q=Pharmaceutical+Issues+when+Crushing%2C+Opening+or+Splitting+Oral+Dosage+. Published 2011. Accessed November 6, 2019.
9. Kurniawan BR. Stabilitas Resep Racikan yang Berpotensi Mengalami Inkompatibilitas Farmasetika yang disimpan Pada Wadah Tertutup Baik. Calyptra. 2013;2(2): 1–16.
10. Jackson M, Lowey A. Handbook of Extemporaneous Preparation. Pharmaceutical Press; 2010. http://www.pharmpress.com/product/9780853699019/pdf/HEP_monograph.pdf. Accessed October 11, 2016.
11. PubChem. Ketotifen fumarate. PubChem. https://pubchem. ncbi.nlm.nih.gov/compound/5282408. Accessed November 6, 2019.
12. Ketotifen. Drugbank. https://www.drugbank.ca/drugs/DB00920. Accessed November 6, 2019.
13. Depatemen Kesehatan Republik Indonesia. Farmakope Indonesia. Edisi V. Jakarta: Departemen Kesehatan Republik Indonesia; 2014.
14. PubChem. Cetirizine hydrochloride. https://pubchem.ncbi.nlm.nih. gov/compound/55182. Accessed November 6, 2019.
15. Cetirizine. Drugbank. https://www.drugbank.ca/drugs/DB00341. Accessed November 6, 2019.
16. PubChem. Cyproheptadine hydrochloride. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/13770. Accessed November 6, 2019.
17. Cyproheptadine. Drugbank. https://www.drugbank.ca/drugs/ DB00434. Accessed November 6, 2019.
18. PubChem. Acetaminophen. https://pubchem.ncbi.nlm.nih.gov/ compound/1983. Accessed November 11, 2019.
19. Acetaminophen. https://www.drugbank.ca/drugs/DB00316. Accessed November 6, 2019.
20. Salbutamol. https://www.drugbank.ca/drugs/DB01001. Accessed November 6, 2019.
21. PubChem. Albuterol sulfate. https://pubchem.ncbi.nlm.nih.gov/ compound/39859. Accessed November 6, 2019.
22. PubChem. Triamcinolone. https://pubchem.ncbi.nlm.nih.gov/ compound/31307. Accessed November 6, 2019.
23. Triamcinolone. https://www.drugbank.ca/drugs/DB00620. Accessed November 6, 2019.
24. Office TS. British Pharmacopoeia. Stationery Office; 2018.
25. Gupta D, Bhatia D, Dave V, Sutariya V, Varghese Gupta S. Salts of therapeutic agents: chemical, physicochemical, and biological considerations. Molecules. 2018;23(7): 1719.
26. Abounassif MA, El-Obeid HA, Gadkariem EA. Stability studies on some benzocycloheptane antihistaminic agents. J Pharm Biomed Anal. 2005;36(5):1011–1018.
27. Borges PF, Lozano PP, Montoya EG, et al. Determination of stress-induced degradation products of cetirizine dihydrochloride by a stability-indicating RP-HPLC method. DARU J Pharm Sci. 2014;22(1):82.
28. Sharaf El-Din MK, Belal F, Tolba MM, Elmansi H. Stability indicating HPLC Method Coupled with Fluorescence Detection for the Determination of Cyproheptadine Hydro-chloride in Its Tablets. Studies on Degradation Kinetics. Anal Chem Lett. 2018;8(4):565–577.
29. Shah D, Patel B, Bhavsar. Stability indicating rp-hplc method for simultaneous estimation of paracetamol and pamabrom in bulk and combined pharmaceutical dosage form. World J Pharm Pharm Sci. 2014;3(4):1009-1020.
30. Kalyani L, Chava V, Rao N. Development and Validation of Stability-indicating RP-HPLC method for the simultaneous analysis of Salbutamol, Theophylline and Ambroxol. Saudi J Med Pharm Sci. 2017:2413–4929.
31. Redasani VK, Tamboli PS, Surana SJ. Development and Validation of a Stability Indicating Rp-Hplc Method for the Estimation of Triamcinolone in Bulk and in Tablet Formulation. J Anal Pharm Res. 2015;1(1):00002.
32. Khan MI, Murtaza G, Sher M, et al. Development and validation of stability indicating assay method of cetirizine hydrochloride by HPLC. Afr J Pharm Pharmacol. 2011;5(2):143–149.
33. Prajapati VD, Jani GK, Khutliwala TA, Zala BS. Raft forming system—An upcoming approach of gastroretentive drug delivery system. J Controlled Release. 2013;168(2):151–165.
34. Gnana Raja M, Geetha G, Sangaranarayanan A. Simultaneous, stability indicating method development and validation for related compounds of ibuprofen and paracetamol tablets by RP-HPLC method. J Chromatogr Sep Tech. 2012;3(8).
35. Nnane IP, Damani LA, Hutt AJ. Development and validation of stability indicating high-performance liquid chromatographic assays for ketotifen in aqueous and silicon oil formulations. Chromatographia. 1998;48(11-12):797–802.
36. Salama F, Attia K, Said R, El-Olemy A, Abdel-raoof A. First Derivative Synchronous Spectrofluorimetric Determination of Cyproheptadine Hydrochloride in Presence of its Oxidative Degradation Product at Critical Micelle Concentration. J Adv Pharm Res. 2018;2(2):104–112.
37. Kulyadi GP, Sathyanarayana MB. Stability indicating HPTLC determination of triamcinalone acetonide in bulk drug and sterile injectable suspension. J Young Pharm. 2016;8(4):430.
38. Dyakonov T, Muir A, Nasri H, Toops D, Fatmi A. Isolation and characterization of cetirizine degradation product: mechanism of cetirizine oxidation. Pharm Res. 2010;27(7):1318–1324.
39. Frag EY, Mohamed GG, Khalil MM, Hwehy M. Potentiometric determination of ketotifen fumarate in pharmaceutical preparations and urine using carbon paste and PVC membrane selective electrodes. Int J Anal Chem. 2011;2011.
40. Veeraiah T, Reddy CVR. Determination of Cyproheptadine hydrochloride in Pure and Pharmaceutical forms: A Spectrophotometric study. Orient J Chem. 2015;31(3):1779.
41. Sant’Anna AM, Hammes PS, Porporino M, Martel C, Zygmuntowicz C, Ramsay M. Use of cyproheptadine in young children with feeding difficulties and poor growth in a pediatric feeding program. J Pediatr Gastroenterol Nutr. 2014;59(5):674–678.
42. Thong MY, Manrique YJ, Steadman KJ. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices. PloS One. 2018;13(3):e0193683.