Quality and Stability Evaluation of Extemporaneously Compounded Losartan Potassium Oral Suspension at the Hospital Pharmacy

Iman M. Alfagih *

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Norah Aloraini

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia and Public Health Authority, Ministry of Health, Riyadh, Saudi Arabia.

Eram Eltahir

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

*Author to whom correspondence should be addressed.


Abstract

Aims: The purpose of this study was to evaluate the quality of an extemporaneous formulation of losartan potassium oral suspensions from crushed losartan potassium tablets to ensure that the compounded suspension maintained its quality attributes during its storage period.

Methodology: Losartan potassium suspensions were compounded extemporaneously in the same way they are prepared for patients at a hospital pharmacy. The suspensions were kept in the refrigerator at 4°C and evaluated immediately and after 9, 18, and 28 days. Suspension ease of redispersion, color, odor, pH, particle size, zeta potential, viscosity, and sedimentation volume were all evaluated. In addition, microbiological stability, drug content, and drug dissolution were assessed.

Results: During the study period, the extemporaneously compounded suspension retained its color and odor, and the pH profile remained consistent. Moreover, all suspensions were easily resuspended in a homogeneous liquid with gentle shaking, and no caking was detected. Furthermore, the results of the microbiological test revealed no microbial growth. The content uniformity and dissolution test results met the pharmacopeial requirements. The findings revealed that the losartan potassium compounding procedure was reliable and capable of producing 2.5 mg/mL of losartan potassium suspension using commercially available tablets and Ora-Blend as a suspending vehicle. Furthermore, after 28 days in the refrigerator (4°C), the suspension had acceptable quality features.

Conclusion: Extemporaneously compounded suspension allows physicians to prescribe a variable dose that adjusts to each patient’s needs, providing treatment when the liquid dosage form is unavailable.

Keywords: Quality control, extemporaneous, losartan potassium, suspension, stability


How to Cite

Alfagih, I. M., Aloraini, N. and Eltahir , E. (2023) “Quality and Stability Evaluation of Extemporaneously Compounded Losartan Potassium Oral Suspension at the Hospital Pharmacy”, Journal of Pharmaceutical Research International, 35(14), pp. 18–28. doi: 10.9734/jpri/2023/v35i147371.

Downloads

Download data is not yet available.

References

Goa KL, Wagstaff AJ. Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. Drugs. 1996;52(4): 820-45.

McIntyre M, Caffe SE, Michalak RA, Reid JL. Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension. Pharmacol Ther. Jan 1997;74(2):181-94.

Shahinfar S, Cano F, Soffer BA, Ahmed T, Santoro EP, Zhang Z et al. A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens. Feb 2005;18(2 Pt 1):183-90.

Webb NJA, Wells TG, Shahinfar S, Massaad R, Dankner WM, Lam C et al. A randomized, open-label, dose-response study of losartan in hypertensive children. Clin J Am Soc Nephrol. Aug 2014;9(8): 1441-8.

Drug lookup | Pediatric care online. American Academy of Pediatrics [cited Oct 10, 2022].

Available:https://publications.aap.org/pediatriccare/drug-monograph/18/5089/ Losartan? autologincheck= redirected?nf Token=00000000-0000-0000-0000-000000000000.

Study of losartan in pediatric patients with hypertension (MK-0954-337). Full Text View: ClinicalTrials.gov [cited Oct 10, 2022]. Available:https://clinicaltrials.gov/ct2/show/NCT00756938

Chu PY, Campbell MJ, Miller SG, Hill KD. Anti-hypertensive drugs in children and adolescents. World J Cardiol. 2014;6(5): 234-44.

Foley L, Toney J, Barlow JW, O’Connor M, Fitzgerald-Hughes D, Ramtoola Z. Investigation of the physical, chemical and microbiological stability of losartan potassium 5 mg/mL extemporaneous oral liquid suspension. Molecules. 2021;26(2) :1-9.

Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs RD. 2013;13(1):1-8.

Brion F, Nunn AJ, Rieutord A. Extemporaneous (magistral) preparation of oral medicines for children in European hospitals. Acta Paediatr. Apr 2003;92(4):486-90.

Giam JA, McLachlan AJ. Extemporaneous product use in paediatric patients: a systematic review. Int J Pharm Pract. 2010;16(1):3-10.

Roark AM, Anksorus HN, Shrewsbury RP. Long-term results of an analytical assessment of student compounded preparations. Am J Pharm Educ. 2014; 78(9):164.

Yuliani SH, Putri DCA, Virginia DM, Gani MR, Riswanto FDO. Prevalence, risk, and challenges of extemporaneous preparation for pediatric patients in developing nations: A review. Pharmaceutics. 2023;15(3):840.

Patel K, Chotai N. Documentation and records: harmonized GMP requirements. J Young Pharm. 2011;3(2):138-50.

Benzi JRde L, Mastroianni PDC. Analysis of extemporaneous oral liquid from commercially available drugs in hospital. Braz J Pharm Sci. 2016;52(3):517-25.

Kristina SA, Wiedyaningsih C, Widyakusuma NN, Aditama H. Extemporaneous compounding practice by pharmacists: A systematic review. Int J Pharm Pharm Sci. 2017;9(2):42.

Greenhalgh LL, dos Passos MMB, Agrizzi AL, de Souza Bustamante Monteiro MS. Compounded medications for cardiovascular use in neonatology: an integrative review. Rev Paul Pediatr. 2023;41.

Allen LV, Popovich NG, Ansel HC. Ansel’s pharmaceutical dosage forms and drug delivery systems. 10th Ed. Philadelphia: Wolters Kluwer; 2012.

Nissen LM, Haywood A, Steadman KJ. Solid medication dosage form modification at the bedside and in the pharmacy of Queensland hospitals. J Pharm Pract Res. Jun 2009;39(2):129-34.

Kulshreshtha AK, Singh ON, Wall GM. Pharmaceutical suspensions: from formulation development to manufacturing. New York: Springer; 2010.

Donnelly RF, Pascuet E, Ma C, Vaillancourt R. Stability of celecoxib oral suspension. Can J Hosp Pharm. 2009;62(6):464-8.

Stanisz BJ, Paszun SK, Zalewska A. Stability of cilazapril in pediatric oral suspensions prepared from commercially available tablet dosage forms. Acta Pol Pharm. 2014;71(4):661-6.

Donnelly RF, Pascuet E, Ma C, Vaillancourt R. Stability of diclofenac sodium oral suspensions packaged in amber polyvinyl chloride bottles. Can J Hosp Pharm. 2010;63(1):25-30.

Ensom MHH, Kendrick J, Rudolph S, Decarie D. Stability of propranolol in extemporaneously compounded suspensions. Can J Hosp Pharm. 2013;66 (2):118-24.

Tran J, Gervase MA, Evans J, Deville R, Dong X. The stability of quetiapine oral suspension compounded from commercially available tablets. Plos One. 2021;16(8, Aug):e0255963.

Alfagih IM, Almurshedi A, Aldosari B, Quadeib BA, Zakaria E, Eltahir E et al. Quality assessment of extemporaneously compounded carvedilol oral suspension for pediatric patients at the hospital pharmacy. J Pharm Res Int. 2022;34:22-31.

Jew RK, Soo-Hoo W, Erush SC, Amiri E. Handbook of Extemporaneous formula-tions: Extemporaneous Formulations for Pediatric, Geriatric, and Special Needs Patients. 3rd Ed. MD: ASHP; 2016.

World Health Organization. Test for sterility. World Heal Organ. 2012;1:571-2.

Santos-Fernández E, Govindaraju K, Jones G. Quantity-based microbiological sampling plans and quality after inspection. Food Control. 2016;63:83-92.

Al-Khawlani Q, Alzomor A, Al-Mekhlafi A. In-vitro quality evaluation of ten diclofenac sodium ampoule brands in Yemen. Res J Life Sci Bioinformatics Pharm Chem Sci. 2018;4:451-63.

The United States pharmacopeia USP 32, the national formulary NF 27. Vol. 1.

Toma MM, de Freitas Santana G, de Nadai TR, Varallo FR, de Lima Benzi JR, de Carvalho Mastroianni P. Extemporaneous compounding: A possible trigger tool to detect potential health incidents. Curr Drug Saf. Oct 2022;17 (3):183-92.

González-González O, Ramirez IO, Ramirez BI, O’Connell P, Ballesteros MP, Torrado JJ et al. Drug stability: ICH versus accelerated predictive stability studies. Pharmaceutics. 2022;14(11).

Mohiuddin AK. Extemporaneous compounding: Cautions, controversies. Innov J Heal Sci. 2019;9(1):252-64.

Sinko JP. Martin’s physical pharmacy and pharmaceutical. 6th ed. Lippincott Williams & Wilkins; 2013.

Jackson A, M, Lowey. Handbook of extemporaneous preparation. 1st Ed. London: Pharmaceutical Press; 2010.

Rahić O, Hadžiabdić J, Tucak A, Sirbubalo M, Hindija L, Elezović A et al. A critical assessment of extemporaneous formulations for proton pump inhibitors: The importance of proper vehicle selection. J Pediatr Pharmacol Ther. 2022;27(7):618-24.

Patel V, Desai T, Chavda B, Katira R. Extemporaneous dosage form for oral liquids. Pharmacophore. 2011;2(2):49-66.

Felton L. Remington essentials of pharmaceutics. 1st ed. London: Pharma-ceutical Press; 2012.

da Silva MRM, Dysars LP, Dos Santos EPd, Ricci Júnior E. Preparation of extemporaneous oral liquid in the hospital pharmacy. Braz J Pharm Sci. 2020;56: 1-15.

Falconer JR, Wu Z, Lau H, Suen J, Wang L, Pottinger S et al. An investigation into the stability and sterility of citric acid solutions used for cough reflex testing. Dysphagia. 2014;29(5): 622-8.

Ratajczak M, Kubicka MM, Kamińska D, Sawicka P, Długaszewska J. Microbiological quality of non-sterile pharmaceutical products. Saudi Pharm J. 2015;23(3):303-7.

Soares Tdos SP, de Souza J, Rosa Lde S, Marques-Marinho FD. Dissolution test for oral suspension: An overview about use and importance. Braz J Pharm Sci. 2022;58:1-27.