A Systematic Review of the Stability of Extemporaneous Pediatric Oral Formulations

Abstract

Background. Extemporaneous compounding is a pharmacy practice to produce suitable pharmaceutical preparations when there are no commercially available, licensed, and age-specific dosage forms. Compared to the use of authorized drugs, these preparations have significant risks. Stability issues are one of the major concerns during the preparation of extemporaneous formulations. Aim. The aim of this work was to study the stability of pediatric extemporaneous formulations of commercially available conventional solid dosage forms by reviewing systematically the currently available stability studies. Method. Articles were searched in the databases of the Web of Science, PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar. From all the searched articles, a total of 28 experimental studies reporting the stability of oral pediatric extemporaneous formulations were included based on the inclusion criteria. Oral extemporaneous formulations from commercially available dosage forms and pure drugs were considered. According to the United States and British Pharmacopeia (USP and BP), most extemporaneous formulations are accepted as chemically stable if they maintain ≥90% of the original drug amount, physically stable if there is no apparent change in physical property, and microbiologically stable if there is no growth of microorganisms in prepared formulations. Finding. In this study, most extemporaneous pediatric oral formulations were chemically, physically, and microbiologically stable and retained more than 90% of the initial content. Very few studies did not include either a physical stability test or a microbiological stability test. Conclusion. According to this systematic review, the chemical and physical instabilities as well as microbial growth on pediatric oral extemporaneous formulations are very rare in published experimental studies. Most studies show that extemporaneous preparations are stable at the ICH recommended storage conditions and duration. Generally, extemporaneously prepared oral formulations will be the promising option for child medications.

Prevalence, Risk, and Challenges of Extemporaneous Preparation for Pediatric Patients in Developing Nations: A Review

“…The toxicological stability can be associated with the minimum toxicity effect. The sterility or resistance toward microbial growth according to the specified requirements can be evaluated to assess the microbiological stability [ 13 , 78 , 79 , 80 ]. A previous study found that the risk of contamination was increased 100-fold in extemporaneous products compounded by nurses or other medical staff compared to those prepared by pharmacists [ 81 ].…”

“…Some extemporaneous preparations are associated with the incidence of adverse events in pediatric patients [ 12 ]. The use of licensed drugs for pediatric patients has the potential to be dangerous, because excipients are not suitable for children, even if administered in small amounts [ 13 ]. Since extemporaneous compounding is described as a branch of pharmacy practice aiming to produce appropriate pharmaceutical preparations when there are no commercially available, licensed, and age-specific dosage forms, problems related to stability, pharmacokinetic profile, and drug effect may potentially occur [ 9 ].…”

“…The challenges of compounding practices should be detailed to allow for the identification of the problems with those procedures. Previous studies have observed several challenges, especially regarding stability and incompatibility, professional knowledge and skill, and regulatory guidance [ 13 , 16 , 17 , 18 ]. In addition, information regarding the stability of compound preparations is still limited [ 17 ].…”

Overcoming Challenges in Pediatric Formulation with a Patient-Centric Design Approach: A Proof-of-Concept Study on the Design of an Oral Solution of a Bitter Drug

“…For that, a linear discriminant analysis (LDA) coupled with the meta-heuristic simulated annealing (SA) variable selection algorithm [30][31][32][33] was implemented. The SA algorithm was used to identify the best sub-set of non-redundant E-tongue sensors [34] which could provide information about the capability of the selected oral formulation to mask the bitterness of the Ra-HCl and to compare it with that of the syrup. The LDA performance was checked for the original grouped data (training) as well as for the leave-one-out cross-validation (LOO-CV) procedure, graphically for the former, based on the 2D plots of the two most significant discriminant functions (DF) and based on the sensitivity values (i.e., the percentage of samples correctly classified into the pre-established groups) for the latter.…”

Efficacy and Safety of Sulfasalazine Suspension in Children With Ulcerative Colitis

“…Suspensions are a liquid form of medication containing finely divided insoluble therapeutically active ingredients dispersed uniformly throughout the suspending medium (47). Suspension can be stable for 30-90 days depending on preparation (48,49). Data on suspensions are quite limited, with only a few formal studies on the palatability and stability of different suspensions reported in the literature (50,51).…”