Shelf life study of extemporaneously prepared omeprazole oral suspension Makeen HA, Pancholi SS, Ali MS, Alam MI, Alam MS, Redaie AM, Albarraq AA, Al-Bratty M, Kadomi YJ, Qasim Attiya MA, Aribi SH

ORIGINAL ARTICLE

Year : 2018 | Volume : 7 | Issue : 1 | Page : 28-32

Shelf life study of extemporaneously prepared omeprazole oral suspension

Hafiz Antar Makeen¹, Shyam Sunder Pancholi², Mohammad Sajid Ali², Mohammad Intakhab Alam², Mohammad Sarfaraz Alam², Ali Mohammed Redaie³, Ahmad A Albarraq¹, Mohammad Al-Bratty⁴, Yahya J Kadomi², Mohammad Ali Qasim Attiya², Salim Hussian Aribi²
¹ Department of Clinical Pharmacy, Pharmacy Practice Research Unit (PPRU), Jazan, Kingdom of Saudi Arabia
² Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Kingdom of Saudi Arabia
³ Department of Pharmacy, King Fahad Central Hospital, Jazan, Kingdom of Saudi Arabia
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Jazan, Kingdom of Saudi Arabia

Date of Web Publication

16-Apr-2018

Correspondence Address:
Hafiz Antar Makeen
College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142
Kingdom of Saudi Arabia

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/sjhs.sjhs_115_17

Abstract

Context: The commercially available oral solid dosage forms are used to prepare suitable liquid dosage forms extemporaneously by the pharmacists for pediatric, geriatric, and other patients with inability of swallowing tablets or capsules. These extemporaneous preparations are not subjected to tests for quality and stability like commercial products. The stability of extemporaneous preparations should be determined in hospital settings, but the practice is to rely on published information. Unavailability of stability data limits the availability of many medicines for special patients. The extemporaneously prepared omeprazole suspension is regularly used in hospital settings. Aim: This research was taken up to perform the stability study of extemporaneous omeprazole oral suspension frequently used in a referral hospital to determine the shelf life. Materials and Methods: Stability studies were performed by keeping the freshly constituted preparations in small containers at 2°C–8°C and 25°C ± 5°C; samples were withdrawn at 0, 7, 14, 21, and 28 days and assayed by spectrophotometric method at 301 nm. The percent degradation or stability was calculated for each preparation, and data were extrapolated to find out the shelf life. Results: It was found that the shelf life (t_90%) of omeprazole oral suspension, prepared extemporaneously, is 32 days at room temperature (25°C ± 5°C) and 54 days in refrigerator (2°C–8°C). Conclusion: Study outcomes shall help the hospital pharmacist to improve pharmaceutical services by dispensing the extemporaneous preparations with the knowledge of their stability and storage condition.

Keywords: Extemporaneous preparation, omeprazole suspension, shelf life, stability study

How to cite this article:
Makeen HA, Pancholi SS, Ali MS, Alam MI, Alam MS, Redaie AM, Albarraq AA, Al-Bratty M, Kadomi YJ, Qasim Attiya MA, Aribi SH. Shelf life study of extemporaneously prepared omeprazole oral suspension. Saudi J Health Sci 2018;7:28-32

How to cite this URL:
Makeen HA, Pancholi SS, Ali MS, Alam MI, Alam MS, Redaie AM, Albarraq AA, Al-Bratty M, Kadomi YJ, Qasim Attiya MA, Aribi SH. Shelf life study of extemporaneously prepared omeprazole oral suspension. Saudi J Health Sci [serial online] 2018 [cited 2022 Jun 27];7:28-32. Available from: https://www.saudijhealthsci.org/text.asp?2018/7/1/28/230227

Introduction

Children represent a vulnerable group for whose treatment many medicines are not available in appropriate dosage form commercially. There are several reasons for unavailability of commercial products for pediatric use. The market for the pediatric drugs is quite limited as compared to that for adults, unless a disease occurs exclusively or frequently in the pediatric population; the large scale production of pediatric formulations is not feasible for pharmaceutical industry. There is greater legal liability and regulatory requirement for commercialization of products that have to be effectively studied in pediatric patients and that amount to additional costs, limited financial returns, and delay in marketing for adults. Currently, there exists an unmet need for design and development of adequate formulations of commonly used pediatric medicines as the pediatric dose cannot be obtained directly by dividing the adult formulations as differences exist between child and adult pharmacokinetic data.^{[1],[2],[3],[4],[5]}

The unlicensed and off-label use of medicine is warranted frequently by the pediatric or geriatric clinician because the commercial oral liquid formulations are not available for therapeutic uses to patients who feel difficulty in swallowing solid dosage forms such as children, elderly persons, and patients on medication by nasogastric or gastrostomy tubes.^[6] Pharmacist in hospital applies traditional compounding methods to produce suitable liquid dosage form; the commercially available tablets are just crushed or capsules are opened and mixed with alcohol, water, simple syrup, or commercially available vehicle (Syrpalta ^®, Orablend ^®).^[7] Commercial suspension vehicles however are to be used with caution as they are not for pediatric use only and may contain excipients that may cause hazardous effects in children. These extemporaneous preparations amount to use of medication in a different indication, dosage, or pharmaceutical form than those mentioned in its marketing authorization.^[8],[9],[10]

The extemporaneous preparations should be esthetically appealing, efficacious, and stable. The instability of the product may involve thermal decomposition, photolytic degradation, hydrolysis, oxidation, and reduction. The decomposition may be caused due to likely interactions between the excipients such as vehicle, stabilizers, buffering agent, flavors, levigating agent, suspending and viscosity building agents as well as closure and container that may have been used during preparation of extemporaneous products. It is common practice to prepare extemporaneous oral liquids from commercially available solid dosage forms such as tablets and capsules due to convenience and availability.^{[11],[12],[13]} The expiry date or shelf life of the extemporaneous preparation in most cases is conventionally assigned on the basis of data published for particular formulation.

The term stability indicates that the dosage unit maintains the chemical identity and strength as well as physical form, while it also includes the ability of the formulation to protect against chances of contamination by microorganisms. The time up to which any formulation will remain stable under recommended conditions of storage is called expiry date. This is the date after which it can be assumed that the product may not be fit for use. The shelf life is the period of time, from the date of manufacture, that a drug product is expected to remain within its approved specification while stored under recommended conditions (>90% of label claim of potency).^{[14],[15],[16]}

The safety and efficacy of extemporaneously prepared liquid dosage forms used in the hospitals is always a great concern, and thus, the scientific study for stability of these products is very important. Proton pump inhibitors are more potent inhibitors of gastric acid secretion as compared to histamine-2 receptor antagonists and thus extemporaneously prepared omeprazole, and pantoprazole suspensions show significantly higher gastric pH alteration as compared to IV pantoprazole.^[17] Omeprazole, a proton pump inhibitor, is commercially available as capsules and used for the treatment of peptic and duodenal ulcers.^[18],[19] Omeprazole is lipophilic in nature and poses a major stability threat, especially in an acidic medium with further degradation in the presence of heat, moisture, solvents, and acidic substances. The suspension of omeprazole turns orange to black on exposure to light, so it should be protected from light.^[20]

The omeprazole suspension for pediatric use in hospital pharmacy setup is commonly prepared from commercially available tablet or capsule formulation of omeprazole approved by the authorities for adult use. There is no published literature available that provide data for stability of such preparation maintained at normal storage conditions till consumption. The objective of the present study was to investigate the shelf life of extemporaneously prepared omeprazole suspension under refrigerated and normal room temperature conditions so as to assure that the preparation dispensed is able to provide the desired dose of drug to the patient till the last administered dose.

Drug profile of omeprazole

IUPAC name: 6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl) methylsulfinyl]-1H-benzimidazole [Figure 1]
Molecular formula: C₁₇H₁₉N₃O₃S
Molecular weight: 345.41606 g/mol
Description: It is a crystalline powder with white to off-white color
Solubility: Very slightly soluble in water, slightly soluble in isopropanol and acetone, while freely soluble in methanol and ethanol
Category: Proton pump inhibitor.

Figure 1: Structure of omeprazole

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Omeprazole suspension prepared extemporaneously is to be taken orally in dose of one mg/kg/day once or twice daily, on an empty stomach to treat conditions such as gastric and duodenal ulcer and Zollinger–Ellison syndrome. However, the manufacturer's recommendation for children below 20 kg is 10 mg once a day and for children above 20 kg is 20 mg once a day.

In this research, omeprazole oral suspension prepared by the pharmacists of a referral hospital, as per the extemporaneous preparation manual, was taken for stability study.

Materials and Methods

The fresh extemporaneously prepared omeprazole oral suspension was collected from the referral hospital. The pure drug omeprazole, used in the present study for preparation of standard curve, was obtained from Sigma chemicals. Other chemical and reagents of analytical grade were procured locally and conformed to pharmacopoeial specifications.

Determination of λ_max

The omeprazole pure drug was dissolved in methanol and then suitably diluted with distilled water and scanned against distilled water in between wavelength 200–400 nm using a ultraviolet (UV)-visible spectrophotometer (Shimadzu 1800) to determine the λ_max[Figure 2].

Figure 2: Ultraviolet scan for determination of λ _maxof omeprazole

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Standard curve of omeprazole

The stock solution of 100 μg/ml strength was prepared in distilled water using small amount of methanol initially as cosolvent and further diluted with distilled water to make standard solutions of the given strength (2, 4, 6, 8, 10 μg/ml). The absorbance of each solution was measured at 301 nm on UV-spectrophotometer [Figure 3].

Figure 3: Standard plot of omeprazole

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Preparation of omeprazole suspension

The omeprazole suspension was prepared as per the extemporaneous preparations manual of the referral hospital. The 2 mg/ml suspension was prepared by emptying 10 capsules of omeprazole (20 mg) in mortar and grinding with 1 g of methyl cellulose and then stirring with sodium bicarbonate solution (8.4%) and making the volume up to 100 ml with the same solution. This was filled in a labeled bottle.

Stability studies

The stability of extemporaneously prepared omeprazole suspension was studied for a period of 4 weeks. The preparations were kept in small containers at room temperature (25°C ± 5°C) and in a refrigerator (2°C–8°C). Samples were withdrawn at frequent time intervals (0, 7, 14, 21, 28 days) and examined for any physical change as well as content of omeprazole was assayed spectrophotometrically. The percent drug remaining at each time point was calculated for each preparation, and a graph of percentage of drug remaining versus time was plotted based on triplicate readings to get degradation rate profile. The shelf life was estimated by extrapolating the graph up to the time when drug concentration will be reduced to 90% under different conditions of storage.

Results and Discussion

The λ_max of omeprazole from the scan was found to be 301 nm [Figure 2]. Absorbance of the standard solution of omeprazole measured at λ_max(301 nm) against water as blank was plotted against the concentrations to construct the linear calibration curve with R² = 0.9976 [Figure 3].

There was no visible change in physical properties in the sample of the extemporaneously made omeprazole suspension kept for stability study under refrigerated and normal room temperature conditions as regard to caking, redispersion behavior, color change, or general appearance during the period of study. It is important to note that though there is likelihood of increased problem of caking for suspensions stored at refrigerated condition as demonstrated in previous studies, there was no such observation in case of omeprazole suspension prepared extemporaneously for the present study due to inclusion of methyl cellulose in formula.^[21]

The chemical stability of the extemporaneous preparation was investigated to improve the therapeutic use and to determine the periods of stable storage or shelf life by measuring the percentage of drug remaining at different time points at the two conditions of storage [Table 1]; the values presented are mean of three determinations expressed as percentage of zero time sample value. The decomposition of sample appears to follow close to zero order kinetics. However, decomposition was faster when the samples were exposed to higher temperature, i.e., in normal room condition (25°C ± 5°C) as compared to that stored in refrigerator at 2°C–8°C [Figure 4]. The standard deviations calculated out of three repeated studies are mentioned in the result. The shelf life (t_90%) of extemporaneously prepared omeprazole oral suspension was calculated graphically by extrapolating the stability plot using equation of regression line and was found to be 32 days at room temperature (25°C ± 5°C) and 54 days at 2°C–8°C. The inclusion of 8.4% solution of sodium bicarbonate as buffering vehicle was responsible for observed stability.

Table 1: Stability of omeprazole stored at different temperatures

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Figure 4: Stability profile of extemporaneous omeprazole suspension

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Conclusion

When an extemporaneous preparation is constituted by the pharmacist in hospital setup to meet the special requirements, it is not sufficient to check the clinical feasibility but a sufficient evidence must be practically generated to demonstrate that the preparation retains all its properties, especially the therapeutically effective dose of the drug during conservation until the point of use by the patient.^[22] There are no published stability data for the omeprazole extemporaneous preparations. The stability studies show that the preparation undergoes degradation when stored at room temperature and also in refrigerated condition. However, the data indicate that the preparation maintains the stability; up to 90% of initial value of drug content is available under both the storage conditions during the period of study. The rate of decomposition is slow in refrigerator as compared to room temperature, and therefore, it is recommended that these extemporaneous preparations should be stored in cool place at 2°C–8°C and can be safely used for up to one month even when stored at room temperature.

Acknowledgment

Authors are thankful to King Fahd Hospital, Jazan for providing the extemporaneous preparation of Omeprazole for study.

Financial support and sponsorship

The study was funded by The Deanship of Scientific Research, Jazan University under Future Scientist Program -3.

Conflicts of interest

There are no conflicts of interest.

References

1.	Nahata MC, Allen LV Jr. Extemporaneous drug formulations. Clin Ther 2008;30:2112-9.
2.	Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE, et al. Developmental pharmacology – Drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349:1157-67.
3.	de Zwart LL, Haenen HE, Versantvoort CH, Wolterink G, van Engelen JG, Sips AJ, et al. Role of biokinetics in risk assessment of drugs and chemicals in children. Regul Toxicol Pharmacol 2004;39:282-309.
4.	Standing JF, Tuleu C. Paediatric formulations – Getting to the heart of the problem. Int J Pharm 2005;300:56-66.
5.	Glass BD, Haywood A. Stability considerations in liquid dosage forms extemporaneously prepared from commercially available products. J Pharm Pharm Sci 2006;9:398-426.
6.	Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr 2005;164:552-8.
7.	Miller JT, Btaiche IF. Oxandrolone in pediatric patients with severe thermal burn injury. Ann Pharmacother 2008;42:1310-5.
8.	Mitchell JF. Oral dosage forms that should not be crushed. Hosp Pharm 1985;20:309-19.
9.	Paradiso LM, Roughead EE, Gilbert AL, Cosh D, Nation RL, Barnes L, et al. Crushing or altering medications: What's happening in residential aged-care facilities? Australas J Ageing 2002;21:123-7.
10.	Wright D. Tablet crushing is a widespread practice but it is not safe and may not be legal. Pharm J 2002;269:132.
11.	VandenBussche HL, Johnson CE, Fontana EM, Meram JM. Stability of levofloxacin in an extemporaneously compounded oral liquid. Am J Health Syst Pharm 1999;56:2316-8.
12.	Winckler SC. Extemporaneous compounding: A return to regulatory limbo? J Pain Palliat Care Pharmacother 2002;16:71-8.
13.	Haywood A, Glass BD. Liquid dosage forms extemporaneously prepared from commercially available products - considering new evidence on stability. J Pharm Pharm Sci 2013;16:441-55.
14.	O'Donnell PB, Bosker AD. Stability of pharmaceutical products. In: Troy DB, editor. Remington the Science and Practice of Pharmacy. 21^st ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 1025-33.
15.	Patrick JS. Martin's Physical Pharmacy and Pharmaceutical Sciences. 6^th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 586-651.
16.	Lachman L, Liberman K, Herbert A. The Theory and Practice of Industrial Pharmacy. Special Indian Edition. New Delhi: CBS Publishers and Distributors Pvt., Ltd.; 2009. p. 772, 777, 849.
17.	Dabiri Y, Fahimi F, Jamaati H, Hashemian SM. The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill-patients. Indian J Crit Care Med 2015;19:21-6. [PUBMED] [Full text]
18.	Quercia RA, Fan C, Liu X, Chow MS. Stability of omeprazole in an extemporaneously prepared oral liquid. Am J Health Syst Pharm 1997;54:1833-6.
19.	Baniasadi S, Kobarfard F, Fahimi F. Extemporaneous preparation and stability assessment of omeprazole suspension in a teaching hospital. Int J Pharm Teach Pract 2012;3:418-21.
20.	Sarisuta N, Tourtip T, Chuarcharoern S. Chemical stability and mechanism of degradation of omeprazole in solution. Thai J Pharm Sci 1998;22:81-8.
21.	Aliabadi HM, Romanick M, Desai S, Lavasanifar A. Effect of buffer and antioxidant on stability of a mercaptopurine suspension. Am J Health Syst Pharm 2008;65:441-7.
22.	Zerbit J, Bordenave J, Benoit G. Physicochemical and microbiological stability studies of a melatonin oral suspension in a commercially available vehicle for pediatric use. Eur J Hosp Pharm 2015;22:89-93.