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Objectives Multiple sclerosis (MS) is a progressive and often debilitating neurological disorder. This chronic disease has a high prevalence in the world and also in Iran. Fatigue is a common symptom of the disease, which causes serious mental and psychological discomfort. Simple saffron syrup, contains some compounds that can be effective in relieving the symptom. The object of this study is to investigate the effect of simple saffron syrup on fatigue in patients with MS. Methods This study is a pre-post study which evaluates the fatigue rate of MS patients (30 participants) according to the FSS scale. The participants were given a saffron simple syrup to consume a tablespoon (7.5 cc) every 8 h for two months. After 60 days of prescribing, patients are assessed for fatigue based on fatigue severity scale (FSS) criteria. Results One-way ANOVA showed that there was a notable difference between the mean score of fatigue in MS patients before and after the intervention (p Conclusions According to the outcomes of this study, simple saffron syrup can be effective as an adjunct therapy for fatigue reduction in patients with MS due to effectiveness besides no significant side effects.

Background and importance Multiple food allergy (MFA), in its severe stage, is a pathology with nutritional and pharmacotherapeutic restrictions. Drug intolerance to available medicines and lack of alternatives can lead to magistral formulations. Aim and objectives To compound oral liquid formulations of iron, zinc and sirolimus by eliminating all preservatives, antioxidants, colourings and flavourings, and evaluate their use in a paediatric patient with MFA. Material and methods We made a literature review including physicochemical characteristics of the active principles studied and the compounding magistral formulations described. We also compared the composition between these commercialised drugs and simple syrups. We accomplished all of the controls described in the pharmacopeia for oral liquid forms on days 1 and 30. Efficacy was evaluated by clinical monitoring from the patient’s birth in 2017. Results According to our bibliographic review, three active principles were formulated with an adjuvant free vehicle: 64% preservative free simple syrup (PFSS). The final composition was: Sirolimus 0.5 mg/mL oral suspension: sirolimus in 1% preservative free carboxymethylcellulose and PFSS. It was compounded using as a pattern the formulation of a tacrolimus suspension, based on molecular similarities. Zinc 5 mg/mL oral solution: zinc acetate dihydrate in sterile water 20% and diluted PFSS, based on existing formulations. We used the best tolerated salt. Iron 30 mg/mL oral solution: ferrous sulfate heptahydrate in sterile water 20% and diluted PFSS. We chose the salt with the highest absorption and solubility. Quality controls: the solutions showed clarity and absence of precipitates and the suspension, re- dispersibility and homogeneity after stirring. The organoleptic characteristics were not optimal for the taste. The results for microbiological controls were negative. Due to the physicochemical and microbiological characteristics, a period of validity of 30 days in refrigerated amber glass was considered. Zinc and iron deficiency were corrected and blood levels of sirolimus were within the adequate range. Currently the patient continues with treatment and an exhaustive follow-up is being carried out. Conclusion and relevance Our oral liquid formulation was appropriate for the pathology of our patient and contributed to his growth and health. The comprehensive pharmaceutical care and an individualised compounding for the MFA was essential. References and/or acknowledgements No conflict of interest.

OBJECTIVES Extemporaneous or magistral formulation of active pharmaceutical ingredients using traditional compounding techniques is a common practice when no commercial form is available for pediatrics. For this vulnerable group of patients, the formulation must be prepared with the minimum quantity and lowest proportion of excipients approved for pediatrics, avoiding the use of preservatives. Often the vehicles used for these preparations are dilutions of simple syrup with water. The objective of this study is to assess the effectiveness of antimicrobial preservation in simple syrup diluted with aqua conservans (conserved water), without propylene glycol or with a reduced proportion of parabens. METHODS The European Pharmacopoeia test of efficacy of antimicrobial preservation was applied to 5 trial vehicles prepared with simple syrup diluted with water. RESULTS Simple syrup is stable during 14 days. Vehicles prepared with simple syrup diluted with purified water did not meet the microbiological quality criteria, but when they are diluted with water that incorporates propylene glycol and parabens (aqua conservans), then they meet the criteria. In addition, if the water is prepared with parabens and without propylene glycol, the criteria for the dilution are met. Nevertheless, if the dilution is done with water prepared with an insufficient proportion of parabens to act as preservatives, the dilution does not meet the pharmacopoeia microbiological criteria. CONCLUSIONS Dilution of simple syrup (50:50 v/v) to prepare a vehicle for extemporaneous or magistral preparation is microbiologically safe when water with methylparaben and propylparaben is used in a proportion of 0.08% and 0.02% (w/w), respectively, avoiding the use of propylene glycol as a solvent and thus its toxic effects in pediatrics.

To determine the physicochemical and microbiological stability of sulfadiazine suspensions (100 mg/mL) in simple syrup (A) and sorbitol (B) formulations prepared from commercially available tablets.An ultra-performance liquid chromatographic assay was developed and validated to determine the chemical stability of sulfadiazine. Three samples were prepared and stored at 5 and 25 °C and assayed at 0, 7, 14 and 30 days. Physical parameters (appearance, pH, particle size and viscosity) were also monitored. Microbiological examination was performed through the suitable counting method.The formulations presented a sulfadiazine concentration of around 95% at the beginning at both temperatures. There was some variation in pH, viscosity and particle size distribution over time. The samples met the pharmacopoeia criteria of microbiological quality over 30 days, but only sulfadiazine formulated in syrup stored at 25 °C was suitable for use after one week.The sulfadiazine suspension in simple syrup was chosen as the most suitable formulation because it demonstrated stability for 14 days at room temperature, providing an alternative liquid dosage form of sulfadiazine for congenital toxoplasmosis treatment.Déterminer la stabilité physicochimique et microbiologique de suspensions de sulfadiazine (100 mg/mL) dans des formulations de sirop simple (A) et de sorbitol (B) préparées à partir de comprimés disponibles dans le commerce. MÉTHODES: Un test de chromatographie liquide ultra-performante a été développé et validé pour déterminer la stabilité chimique de la sulfadiazine. Trois échantillons ont été préparés et stockés à 5 ºC et à 25 ºC et analysés à 0, 7, 14 et 30 jours. Les paramètres physiques (apparence, pH, granulométrie et viscosité) ont également été contrôlés. Un examen microbiologique a été effectué par la méthode de comptage appropriée. RÉSULTATS: Les formulations présentaient une concentration en sulfadiazine d'environ 95% au début aux deux températures. Il y avait une certaine variation du pH, de la viscosité et de la distribution de la taille des particules au fil du temps. Les échantillons répondaient aux critères de pharmacopée pour la qualité microbiologique aprè 30 jours, mais seule la sulfadiazine formulée dans du sirop conservé à 25 ºC pouvait être utilisée après une semaine.La suspension de sulfadiazine dans un sirop simple a été choisie comme la formulation la plus appropriée car elle a démontré une stabilité à 14 jours à température ambiante, fournissant une forme galénique liquide alternative de sulfadiazine pour le traitement de la toxoplasmose congénitale.

Background Flecainide acetate (FlecAc) is an antiarrhythmic drug, effective in children and fetal tachyarrhythmias. FlecAc is commercially available as 50 mg–150 mg oral tablets or intravenous injectable solutions, approved only for use in adults. For paediatric use, an extemporaneous preparation has to be compounded, using the pure active principle or, when this is lacking, the ground tablet. Few examples of extemporaneous FlecAc preparations are reported in the literature, normally at a dose of 20 mg/mL. Nevertheless, in the case of neonates and infants, a lower concentration is useful. Purpose The aim of this work was to compound FlecAc oral liquids (2 mg/mL) using pure powder (API) or ground commercial tablets (GCT) and to evaluate the chemical stability of the active principle. Material and methods Oral solutions were compounded using either a preserved simple syrup (PSS) with the addition of a suspending phase or a ready-to-use commercial suspending vehicle, ORA-Plus ORA-Sweet (OPOS), to be stored at 4°C or 25°C, respectively. Four types of aqueous solutions were compounded following hospital standard operating procedures. In three different pharmacies, seven hospital pharmacists compounded a total of 28 preparations (n=28): 1) PSS-API, 2) PSS-GCT, 3) OPOS-API and 4) OPOS-GCT. The samples were stored at 4°C (PSS), 25°C (OPOS) and 40°C (both) for 42 days. The FlecAc content was determined using a stability indicating the high-performance liquid chromatography method. Results At time t=0, the mean FlecAc content of all samples was 1.82±0.10 mg/mL, against a labelled content of 2.00 mg/mL. A significant difference in FlecAc content was observed only in the case of GCT preparations (OPOS-GCT: 1.87±0.07 mg/mL; PSS-GCT: 1.79±0.15 mg/mL, p=0.03). Based on these results, duration and method of stirring were further investigated and improved in a second batch, which showed a higher mean content and reduced variability (1.92±0.06 mg/mL). FlecAc was stable over the entire period. Conclusion FlecAc is completely solubilised in the proposed vehicles and stable for 42 days. A suspending agent is therefore necessary only to mask the excipients of the tablet, if not completely solubilised. Normally suggested storage in a refrigerator when PSS is compounded should be carefully considered, because of the influence of the reduced temperature on FlecAc solubility. References and/or acknowledgements No conflict of interest.

Background Primary bladder neck obstruction (PBNO) is a failure in which the bladder neck does not open appropriately or completely during voiding. α-Blocker together with anticholinergics are the pharmacological therapy that has shown some benefit in children. Off-label therapy with prazosin and oxybutynin was proposed in two neonates with PBNO. Purpose To compound oxybutynin and prazosin correctly for dosing and administration in these patients and monitoring them. Material and methods A bibliographic search of indication, dosage and formulation was made in Pubmed, Micromedex and other compounding pharmaceutical sources. Keywords: prazosin, oxybutynin, neonate, PBNO. Clinical monitoring and interviews were carried out with the parents of two neonates (5 and 12 months’ old) in treatment from the first month of life to the present. Results We did not find any bibliographic reference describing its use in neonates. Initially, we formulated sachets with their specific dose. Later, we formulated in suspension, 100 mcg/ml prazosin and 1 mg/ml (minurin) and oxybutynin (raw material), using simple syrup without preservatives as a vehicle. The initial doses collected were the minimum referenced in children: 10 mcg/kg/12 hour for prazosin and 0.1 mg/kg/12 hour for oxybutynin. The dose of prazosin was increased weekly, in both neonates, because of the improvement in uro-dynamics tests and no significant adverse effects detected. It was increased until 25 mcg/kg/8 hour (maximum collected in paediatrics 25 mcg/Kg/6 hour). The dose of oxybutynin was maintained in one patient with the initial dose and, in another, rose to 0.1 mg/kg/8 hour (the maximum 0.2 mg/kg/8 hour). Pharmaceutical care was performed by the explanation of the doses in milliliters adjusted to the weight and monitoring of possible adverse effects. Strawberry essence was incorporated into the suspension to improve flavour. Since birth, the number of catheters has decreased, with an improvement in the patient’s symptoms. Regarding safety, no adverse reactions attributable to the drugs have been observed. Conclusion Both oral suspensions were appropriated for the pathology of our patients, which continue in treatment. They are well tolerated, for an age range not included in the bibliography, with good response. Pharmaceutical care was given from the beginning to the family and the paediatric service. References and/or acknowledgements To Rosa Millan Garcia for the review of the work and her contribution to it. No conflict of interest.

Background As many medicines are not available for paedriatic use they have to be elaborated in the pharmacy service. Generally, there are different formulations described in the bibliography. Purpose To compare two liquid formulations of omeprazole elaborated in the pharmacy service of a tertiary hospital evaluating physicochemical stability and organoleptic characteristics (OC) with the aim of defining the most ideal formulation. Material and methods A bibliographic check of the different formulations of omeprazole was carried out and two liquid magistral preparations were elaborated in triplicate. Formulation 1 was prepared from omeprazole monohydrate salt, using as excipients: simple syrup, mixture conservans and purified water. Formulation 2 was prepared from omeprazole capsules using bicarbonate 1 M as excipient. Conditions of refrigeration and of light protection were established. As an indicator of physicochemical stability, the pH was selected. For its determination a pH measurer, Mettler Toledo SevenMulti was used. The data was analysed using an Excel 2010 spreadsheet. The results were expressed as average ±SD. Also colour, smell and taste (OC) were evaluated, as well as homogeneity of the formulations. Thirty days was established as a period of study. The determinations were carried out on days 0,10,17,24 and 30 post-elaboration. Results The pH was stable with barely any oscillations during the period of study. The data obtained for formulation 1 was: 8.476±0.012 (sample 1), 8.544±0.01 (sample 2) and 8.547±0.018 (sample 3). For formulation 2 it was: 6.777±0.026 (sample 1), 6.373±0.005 (sample 2) and 6.382±0.003 (sample 3). The homogeneity of the formulations remained stable. The OC fluctuated significantly during the period of study. The colour of formulation 1 evolved from amber and opaque to dark brown, and the smell evolved from sweet to metallic and the taste (bitter-sweet) remained stable. In formulation 2 the opaque white colour and the disagreeable metallic smell remained unchanged. The taste changed, from very bitter to salty. Conclusion In both formulations the pH remained stable. The formulation based on raw material presents significant changes in OC, mainly in colour. With regard to the formulation whose elaboration is made from capsules, the OC remained more stable. As a result of this, it was decided to establish formulation 2 as a preferential formula in spite of its more disagreeable taste. References and/or acknowledgements No conflict of interest.

Although beet and cane sugar sources have nearly identical chemical compositions, the sugars differ in their volatile profiles, thermal behaviors, and minor chemical components. Scientific evidence characterizing the impact of these differences on product quality is lacking. The objective of this research was to determine whether panelists could identify a sensory difference between product matrices made with beet and cane sugar sources. Sixty-two panelists used the R-index by ranking method to discern whether there was a difference between 2 brands of beet and 2 brands of cane sugars in regard to their aroma and flavor, along with a difference in pavlova, simple syrup, sugar cookies, pudding, whipped cream, and iced tea made with beet and cane sugars. R-index values and Friedman's rank sum tests showed differences (P < 0.05) between beet and cane sugars in regard to their aroma and flavor. Significant differences between the sugar sources were also identified when incorporated into the pavlova and simple syrup. No difference was observed in the sugar cookies, pudding, whipped cream, and iced tea. Possible explanations for the lack of difference in these products include: (1) masking of beet and cane sensory differences by the flavor and complexity of the product matrix, (2) the relatively small quantity of sugar in these products, and (3) variation within these products being more influential than the sugar source. The findings from this research are relevant to sugar manufacturers and the food industry as a whole, because it identifies differences between beet and cane sugars and product matrices in which beet and cane sugars are not directly interchangeable.

Sildenafil citrate, neonatal pulmonary antihypertensive, not being marketed as a pediatric drug, an extemporaneous liquid preparation of this drug could be proposed for a pediatric use. The objective of this study is therefore to prepare a solution of Sildenafil citrate, in a simple syrup (1.25 mg/ml), from Sildenafil Tablets (VIACTAL® 50 mg), according to a common practice “dosage adjustment” allowing to adjust doses in pediatrics. A physicochemical and microbiological stability study of this solution was carried out at 5 °C. The results of this study have shown that Sildenafil citrate syrup solutions stored in the refrigerator are stable for a period of 04 weeks: unchanged color and odor, no crystallization observed, no pH variation, unchanged active substance concentration and no microbial contamination detected. However, after opening the vials, these preparations must be used within 07 days.

The purpose of this study was to determine the stability of the pH sensitive drug, omeprazole, within different solid oral pharmaceutical formulations and to determine whether the addition of antacid and surfactant agents, at varying concentrations, influenced drug stability and release. Spectrophotometric and chromatographic techniques were used for evaluation purposes, giving good results concerning linearity, precision and specificity within the range of concentrations used in this study. However, the results show that the degradation products of omeprazole interfere with spectrophotometric evaluation, making this technique insufficiently selective for omeprazole. On the other hand, liquid chromotography proved to be more sensitive, accurate and precise. Additionally, in an attempt to improve the administration form of the drug, an extemporaneous suspension was designed, which after evaluation proved to be a satisfactory administration vehicle. The best formulation of omeprazole studied is: omeprazole: 0.5%; corn starch 34.2%; aluminum hydroxide 26%; magnesium hydroxide 13%; simple syrup 24.8%; SDS 1%.

Objective—To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days. Design—Prospective study. Sample Population—Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively. Procedures—Preparations were stored at approximately 4°C (39.2°F) or 22°C (71.6°F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated. Results—In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained ≥ 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 ± 0.04 and 0.21 ± 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22°C for 28 days yielded bacterial growth. Conclusions and Clinical Relevance—DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Levocarnitine chloride is used for the therapeutic purpose of levocarnitine deficiency. For infants, however, levocarnitine chloride tablets must be crushed to avoid difficulties associated with swallowing, and also to administer an appropriately low dosage. Since the tablet is extremely hygroscopic and sour, it is dissolved in water containing simple syrup after crushing. In this study we investigated the stability of the drug after dissolution to optimize its preparation for clinical use. It was shown to be stable for at least 90 days after preparation, and microbes did not grow in 1-10% (w/v) solutions (pH 2.0-2.5) regardless of the presence or absence of simple syrup. Furthermore, the autoclaved levocarnitine chloride solution was as stable as the non-autoclaved one. In conclusion, the method employed in our hospital for the preparation of levocarnitine chloride for infants is appropriate and is recommended as a standard medicine supply method among different facilities.

Purpose. The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously prepared oral suspensions stored at 4 and 25 °C was studied. Methods. Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions. Five plastic bottles of each suspension were stored in amber plastic prescription bottles at 4 or 25 °C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of sildenafil content by high-performance liquid chromatography; pH was also measured. Samples were visually observed against black and white backgrounds. Results. The mean concentration of sildenafil citrate exceeded 98% of the initial concentration in all samples at both temperatures throughout the 91-day study period. No changes in pH, odor, or physical appearance were observed. Conclusion. Sildenafil citrate 2.5 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in plastic prescription bottles at 4 and 25 °C.

Triclofos sodium syrup (Tricloryl® syrup) is mainly used for pretreatment in EEG examinations and sedation before CT and MRI. The unpleasant taste of the syrup, however, occasionally causes compliance problems with children. As we had also experienced difficulties in obtaining sufficient supplies of this medicine for a few months, we prepared a chloral hydrate syrup in our hospital as a substitute for triclofos sodium syrup, aiming to reduce the unpleasant taste and smell of chloral hydrate in the process. Stability and sterility were also investigated. The results of a taste test in healthy volunteers showed that the taste and smell of a 4% chloral hydrate syrup were improved by using an apple flavor, aspartame and a simple syrup base. In our stability and sterility study under the storage condition of 4°C with shading over 6 months, the potency of the syrup was maintained (95 %) and there was no bacterial contamination. These results suggest that the 4% chloral hydrate syrup prepared in our hospital as a substitute for triclofos sodium syrup could improve the compliance of children.

We investigated the stability of “Chloral Hydrate Syrup” by 1H-NMR spectrometry and spectrophotometry.“Choloral Hydrate Syrup” is composed of 4%(w/v) chloral hydrate, 50%(w/v) simple syrup and 2%(w/v) pineapple flavor. When “Chloral Hydrate Syrup” was kept in the dark and cold conditions, chloral hydrate was found to be stable for at least 2 weeks. No changes in the smell and taste of “Chloral Hydrate Syrup” were observed. However, the color was fugitive, and 80% of original color was lost within a week even in the dark and cold conditions.The Pharmacological effects of “Chloral Hydrate Syrup” given for 25 infant patients, who had been hospitalized in Toyama Medical and Pharmaceutical University Hospital between September and November 1997, were evaluated clinically. “Chloral Hydrate Syrup” showed a certain, hypnotic effect in 24 out of 25 patients. These results suggest that “Chloral Hydrate Syrup” is useful as a hospital hypnotic preparation.

Objective To determine the stability of nifedipine in two oral suspensions stored at 4°C and 25°C in plastic prescription bottles over a 3-month period. Design Two suspensions were prepared: 1% methylcellulose:simple syrup NF (1:13) stored in ten 2 oz bottles; and Ora Plus:Ora Sweet (1:1) at a nifedipine concentration of 4 mg/mL also stored in ten 2 oz bottles. Five bottles of each formulation were stored at 4°C, and the rest of the bottles were stored at 25°C. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating high-performance liquid chromatography analytic method (n = 15). Setting Laboratory. Results At 4°C, the mean concentration of nifedipine was nearly 100% that of the original concentration in both the Ora Plus–Ora Sweet and the 1% methylcellulose–syrup formulations during the 3-month study period. At 25oC, the mean ± standard deviation concentration of nifedipine was 98.9% ± 2.36% of the initial concentration in the Ora Plus–Ora Sweet and 97.4% + 2.48% in the 1% methylcellulose–syrup formulation over the 3-month period. No changes in pH or physical appearance were observed. Conclusion Nifedipine can be prepared in two liquid dosage forms and stored for up to 3 months under refrigeration or at room temperature.

Background: Cyclophosphamide, an alkylating agent, is widely used for the treatment of many adult and pediatric malignancies. The stability of cyclophosphamide in aqueous- and methylcellulose-based oral suspending vehicles is currently unknown. Objective: To develop and validate a stability-indicating high-performance liquid chromatography (HPLC) method to measure cyclophosphamide concentrations in simple syrup and Ora-Plus, and assess the 56-day chemical stability and physical appearance of cyclophosphamide in these suspensions at both room temperature (22 °C) and 4 °C. Methods: The intravenous formulation of cyclophosphamide was diluted to 20 mg/mL in NaCI 0.9%, compounded 1:1 with either suspending vehicle, and stored in the dark in 3-mL amber polypropylene oral syringes at 4 °C and 22 °C. Aliquots from each syringe were obtained on days 0.3, 7, 14, 21, 28, 35, 42, 49, and 56 and assayed using the validated stability-indicating HPLC-UV method. A C18 analytical column was used to separate cyclophosphamide from the internal standard, ifosfamide, with a mobile phase of 21% acetonitrile in 79% sodium phosphate buffer. The suspension was examined for odor change, visually examined under normal fluorescent light for color change, and examined under a light microscope for evidence of microbial growth. Results: Samples of cyclophosphamide in both simple syrup and Ora-Plus were stable when kept at 4 °C for at least 56 days. At room temperature, cyclophosphamide in simple syrup and Ora-Plus had a shell life of 8 and 3 days, respectively. No changes in color or odor or evidence of microbial growth were observed. Conclusions: Cyclophosphamide can be extemporaneously prepared in simple syrup or Ora-Plus and stored for at least 2 months under refrigeration without significant degradation.

The stability of clonidine hydrochloride in an extemporaneous oral liquid formulation refrigerated for 28 days was studied. A suspension was prepared by grinding commercially available 0.2-mg clonidine hydrochloride tablets, adding Purified Water, USP, to form a paste, and then adding Simple Syrup, NF. A control solution was prepared from analytical grade clonidine hydrochloride powder in Simple Syrup, NF. The final concentration of clonidine hydrochloride in both formulations was 0.1 mg/mL. Three samples of each preparation were stored in 2-ounce amber glass prescription bottles in the dark at 4 degrees C. Immediately after preparation and at 3, 7, 14, 21, and 28 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. On day 28, the mean percentages of the initial clonidine hydrochloride concentrations remaining were 92.4% in the suspension and 93.7% in the solution. The color, odor, and pH of the samples did not change appreciably over the study period. An extemporaneously compounded oral liquid preparation of clonidine hydrochloride in Simple Syrup, NF, is stable under the conditions studied for up to 28 days.

OBJECTIVE: Dapsone use in pediatric patients is increasing; however, the currently available tablet dosage form cannot be used in young children. The objective of our study was to determine the stability of dapsone in two oral suspensions stored at two temperatures. METHODS: Commercially available dapsone tablets (25 mg) were used to prepare the suspensions: the first in simple syrup and water with citric acid, the second in 1:1 Ora Sweet:Ora Plus to yield a concentration of 2.0 mg/mL. The dosage forms were stored in 10 amber plastic prescription bottles. Five were stored at 25 °C and five at 4 °C. Three samples were taken from each of five bottles at 0, 7, 14, 28, 42, 56, 70, and 91 days (n = 15). Dapsone concentrations in each sample were measured in duplicate by a validated and stability-indicating HPLC method; the pH of each sample was also determined. The drug was considered stable if the mean concentration ≥90% of the original concentration. RESULTS: The mean concentrations of dapsone were >95% of the initial concentrations for 91 days at both 4 °C and 25 °C in each suspension. There was a slight darkening of the samples stored at 25 °C. CONCLUSIONS: Dapsone was stable in two suspensions prepared from commercially available tablets for at least three months at 4 °C and 25 °C.

The stability of propylthiouracil in two extemporaneously prepared suspensions at 4 and 25 degrees C was studied. Commercially available 50-mg propylthiouracil tablets were used to prepare suspensions in 1:1 Ora-Sweet:Ora-Plus and in 1:1 1% methylcellulose:Simple Syrup, NF, to yield a propylthiouracil concentration of 5 mg/mL. Each suspension was stored in 10 amber plastic prescription bottles, 5 of them at 4 degrees C and the other 5 at 25 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days for assay by stability-indicating high-performance liquid chromatography. More than 90% of the initial propylthiouracil concentration was retained in both suspensions for 70 days at 25 degrees C and for 91 days at 4 degrees C. There were no changes in physical appearance, color, or odor, and the pH remained essentially unchanged. Propylthiouracil 5 mg/mL in two extemporaneously prepared oral suspensions was stable for at least 70 days at 25 degrees C and for at least 91 days at 4 degrees C.

Labetalol hydrochloride (HCl) is an effective antihypertensive drug. It is available in a tablet dosage form, which may be difficult to administer to geriatric and pediatric patients. The tablets can be suspended in various liquid vehicles, but its stability under these conditions is unknown. The objective of our study was to determine the stability of labetalol HCl in five liquid vehicles, in both plastic and glass prescription bottles, over a four-week period at room temperature and under refrigeration. Labetalol HCl tablets (Trandate, Glaxo) were triturated, and suspended in distilled water, simple syrup, apple juice, grape juice, and orange juice to approximate concentrations of 7–10 mg/mL. After filtration, the liquids were stored in five amber, plastic prescription bottles, and five amber, glass prescription bottles at 4°C and 23°C. The samples were collected at 0, 24, and 72 hours, and 1. 2, and 4 weeks after initiation of the study. Labetalol HCl was measured by an HPLC method. Because there was no substantial change in labetalol HCl concentration during the study period, the tablet dosage form can be reformulated, stored, and administered to elderly or pediatric patients as a liquid dosage form.

Background Mercaptopurine is indicated for the treatment of acute lymphoblastic leukaemia (ALL). In our country, there is no commercial presentation that allows proper dosage in paediatric patients. However, in March 2012, an expensive 20 mg/mL mercaptopurine suspension (100 mL) that may be purchased as a foreign drug was commercialised. In order to meet the needs of these patients using a more cost effective alternative, the pharmacy department developed a mercaptopurine compounded drug. Purpose To assess the economic impact of the development of a 50 mg/mL mercaptopurine suspension (12 mL) compared with the use of a commercial syrup. Material and methods Mercaptopurine suspension is compounded by adding simple syrup, cherry syrup and sterile water for irrigation to 50 mg of mercaptopurine triturated tablets. It is prepared in a biological safety cabinet, packed in amber glass bottles and its shelf life is 28 days. This was a retrospective study from March 2012 to September 2015. Collected data, from Farmatools and Farmis software, were: number of ALL patients treated with the suspension, number of suspensions dispensed, number of mercaptopurine tablets used and its cost, and treatment phase of the ALL-SEHOP-PETHEMA protocol when the dispensation was done. Mercaptopurine suspension appraisal was done according to the valuation rules of the Regional Health Management. The Ministry of Health website was consulted for the commercial suspension price. Total savings by the development of a compounded medicine instead of buying the commercial presentation was established by comparing the direct costs between both alternatives. Results During the study period, 40 mercaptopurine suspensions were prepared to treat 3 patients (according to the ALL-SEHOP-PETHEMA protocol, 2 suspensions were dispensed for the consolidation phase of the treatment and 38 for the maintenance phase). Each one cost 28.1€ (16.6€ mercaptopurine suspension, 0.3€ storage, 11.2€ professional fees); total expenditure was 1124€. Each commercial suspension costs 269.36€ and its shelf life is 56 days; total expenditure would have been 5387.2€. Cost savings achieved by developing the mercaptopurine suspension instead of buying the commercial presentation was 4263.2€. Conclusion The compounded 50 mg/mL mercaptopurine suspension can meet the therapeutic needs of ALL paediatric patients and save costs. It would be useful to assess the addition of a preservative to the compounded suspension to increase its shelf life and save on costs. No conflict of interest.

Background Commercial presentations of oral thioguanine suitable for dosing in paediatric patients diagnosed with acute lymphoblastic leukaemia (ALL) are not available in our country. Therefore, paediatricians in our hospital requested the pharmacy department to develop an oral thioguanine compounded medicine. Purpose To develop a standard operating procedure (SOP) for an oral thioguanine compounded medicine suitable for treating paediatric patients diagnosed with ALL. Material and methods In order to establish the most suitable formulation characteristics (composition, elaboration methods, stability, packaging materials and storage conditions) a bibliographic review of several databases was done (PubMed and Micromedex Health-Care). This research also included Trissel’s Stability of Compounded Formulations Paediatric Dosage Handbook and several paediatric hospital websites. Results Based on the results, an SOP was designed to prepare a thioguanine suspension, in accordance with the general procedure for preparation of suspensions (PN/L/FF/008/00) of the National Formulary. Name: thioguanine 40 mg/mL suspension, 20 mL. Ingredients: thioguanine (800 mg; thioguanine 40 mg tablets are used), sterile water for irrigation (4 mL), methylcellulose 1% (7 mL), simple syrup (qs 20 mL). Equipment needed: 5 mL, 10 mL and 20 mL syringes, beaker, stir bar, plugs.-Packaging: amber glass prescription bottle. Modus operandi: suspension is prepared in a biological safety cabinet. The required volume of sterile water, methylcellulose and simple syrup is loaded into separate syringes and placed inside the cabinet, along with a 20 mL empty syringe and thioguanine tablets. Thioguanine is dissolved in water (without triturating the tablets, it could take between 15–20 min). Once completely dissolved, methylcellulose is added and stirred gently. This suspension is loaded into the empty syringe and diluted to 20 mL with simple syrup. The suspension is transferred to the prescription bottle and then properly shaken. The final suspension has a light yellow colour and pleasant organoleptic characteristics. Labelling: 40 mg/mL thioguanine suspension (20 mL). Administration: oral. Conservation: ambient temperature, protected from light. Shelf-life: 30 days. Shake before use. Indication: acute lymphoblastic leukaemia Conclusion The SOP for the preparation of thioguanine 40 mg/mL oral suspension is simple and the designed compounded medicine has allowed the administration of the required dose, covering the therapeutic needs of paediatric patients diagnosed with ALL. No conflict of interest.

Summary Objective: An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. Methods: Suspensions (0·5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus® and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22–26 °C and evaluated weekly. Results: The volume mean diameter d(4,3) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. Conclusion: The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.

The stability of pyrimethamine in a liquid dosage formulation stored for up to three months was studies. Commercially available 25-mg pyrimethamine tablets were crushed with a mortar and pestle and mixed with a 1:1 mixture of Simple Syrup, NF, and 1% methylcellulose to yield a suspension with a pyrimethamine concentration of 2 mg/mL. The suspension was poured into 10 amber plastic and 10 amber glass prescription bottles; 5 plastic and 5 glass bottles were stored at 4 degrees C, and the remaining bottles were kept at 25 degrees C. Samples were collected at intervals up to 91 days and tested for pyrimethamine concentration by stability-indicating high-performance liquid chromatography. Pyrimethamine remained stable throughout the three-month study period under all conditions. At 4 degrees C, pyrimethamine concentrations remained above 96% of the initial concentration; at 25 degrees C, pyrimethamine concentrations remained above 91%. No substantial changes in pH were observed. Pyrimethamine was stable for at least 91 days in an oral suspension stored in plastic or glass prescription bottles at 4 or 25 degrees C.

BACKGROUND Lisinopril is used in pediatric patients with hypertension. It is not commercially available as a liquid. Little is known about the stability of lisinopril in extemporaneously prepared liquid dosage forms. OBJECTIVE To determine the stability of lisinopril in 2 oral suspensions stored at 4 and 25 °C in plastic prescription bottles. METHODS Five bottles contained methylcellulose 1%:simple syrup NF (1:13) and the other 5 bottles had Ora Plus–Ora Sweet (1:1) at a lisinopril concentration of 1 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by stability-indicating HPLC analytical method (n = 15). RESULTS At 4 °C, the mean ± SD concentration of lisinopril remained >95.1 ± 1.8% of the initial concentration in the methylcellulose formulation and 95.1 ± 3.2% of the initial concentration in the Ora Plus–Ora Sweet formulation throughout the 91-day study period. At 25 °C, the mean concentration of lisinopril remained >92.4 ± 2.2% of the initial concentration in the methylcellulose formulation for 8 weeks and 95.8 ± 2.3% of the initial concentration in the Ora Plus–Ora Sweet formulation throughout the 91-day study period. No changes in physical appearance in any samples were seen during this period CONCLUSION Lisinopril can be prepared in either of 2 liquid dosage forms and stored for at least 13 weeks under refrigeration and 8 weeks at room temperature.

The stability of ursodiol in an extemporaneous oral liquid formulation refrigerated at 4 degrees C for 35 days was studied. A suspension was prepared by opening commercially available 300-mg capsules of ursodiol, adding Glycerin, USP, to form a paste, and then adding Simple Syrup, NF. A control solution was prepared from analytical-grade ursodiol powder in simple syrup. The final concentration of ursodiol in both formulations was 60 mg/mL. Three samples of each preparation were stored in 2-oz, amber glass prescription bottles in the dark at 4 degrees C. Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. Stability was defined as the retention of more than 90% of the initial concentration. On day 35, the mean percentage of the initial ursodiol concentration remaining was 96.5% in the suspension made from powder-filled capsules, and 100.6% in the suspension made from analytical-grade powder. The color, odor, and pH of the samples did not change appreciably over the study period. An extemporaneously compounded oral liquid preparation of ursodiol in simple syrup was stable under the conditions studied for up to 35 days.

BACKGROUND: Sotalol is used in certain pediatric patients to treat, suppress, or prevent the recurrence of life-threatening ventricular arrhythmias. However, it is commercially unavailable in a liquid dosage form. The use of an extemporaneously prepared liquid dosage form must be supported by the documentation of the chemical and physical stability of sotalol. OBJECTIVE: To determine the stability of sotalol hydrochloride extemporaneously prepared from tablets in 2 oral suspensions stored at 2 temperatures. METHODS: Five bottles contained Ora Plus: Ora Sweet (1:1) and the other 5 bottles had 1% methylcellulose:simple syrup NF (1:9), with a sotalol concentration of 5 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating HPLC analytical method (n = 15). RESULTS: At 4°C, the mean concentration of sotalol was at least 98.9% of the original concentration in Ora Plus: Ora Sweet suspension and 95.5% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. At 25°C, the mean concentration of sotalol was ≥95.5% of the original concentration in Ora Plus: Ora Sweet suspension and 94.4% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. The pH did not change substantially during the study period. Further, no changes in physical appearance were seen during the study. CONCLUSIONS: Sotalol hydrochloride can be prepared in either of 2 liquid dosage forms and stored in plastic bottles for 13 weeks at 4 or 25°C without substantial loss of potency.

The stability of isradipine in an extemporaneously compounded oral liquid was studied. A suspension was prepared from the powder of commercially available 5-mg isradipine capsules and sufficient Simple Syrup, NF, to make a final volume of 50 mL. A control suspension was prepared from analytical-grade isradipine powder and Simple Syrup, NF. The final concentration of isradipine in both suspensions was 1 mg/mL. Three identical volumes of each suspension were stored in 2-oz amber glass prescription bottles, which were stored at 4 degrees C. Immediately after preparation and at 7, 16, 22, 28, and 35 days, samples were visually inspected and assayed in duplicate by high-performance liquid chromatography; the pH of the samples was also determined. At least 95% of the initial isradipine concentration remained throughout the study period in all samples of both suspensions. Color, odor, and pH did not change appreciably. Isradipine 1 mg/mL in an oral liquid compounded from Simple Syrup, NF, and powder from capsules was stable for at least 35 days in amber glass bottles at 4 degrees C.

The stability of baclofen in an extemporaneously compounded oral liquid formulation for 35 days was studied. A suspension was prepared by grinding commercially available 20-mg baclofen tablets and adding Glycerin, USP, to form a paste. Simple Syrup, NF, was added as necessary to make a final volume of 60 mL. A control solution was prepared from analytical-grade baclofen powder in Simple Syrup, NF. The final concentration of baclofen in both formulations was 5 mg/mL. Three samples of each preparation were stored in 2-oz, amber glass prescription bottles in the dark under refrigeration at 4 degrees C. Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. On day 35, the mean percentages of the initial baclofen concentrations remaining were 95.9% in the suspension and 95.6% in the solution. The color, odor, and pH of the samples did not change appreciably over the study period. In an extemporaneously compounded oral liquid preparation in Simple Syrup, NF, stored in the dark under refrigeration, baclofen was stable for at least 35 days.

The stability of terbutaline sulfate in an extemporaneous oral liquid formulation refrigerated for 55 days was studied. A suspension was prepared by grinding commercially available 5-mg terbutaline sulfate tablets, adding Purified Water, USP, to form a paste, and then adding Simple Syrup, NF. A control solution was prepared from analytical grade terbutaline sulfate powder in Simple Syrup, NF. The final concentration of terbutaline sulfate in both preparations was 1 mg/mL. Three samples of each formulation were stored in 4-ounce amber glass prescription bottles in the dark at 4 degrees C. Immediately after preparation and at 10, 19, 35, and 55 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. On days 0 and 35, 100-microL samples of each suspension and solution were placed on agar plates for microbiological testing. On day 55, the mean percentages of the initial terbutaline sulfate concentrations remaining were 103.8% in the suspension and 91.7% in the solution. Color, odor, and pH of the samples did not change appreciably, and colony counts of bacteria were within acceptable limits. An extemporaneously prepared liquid preparation of terbutaline sulfate in Simple Syrup, NF, is stable under the conditions studied for up to 55 days; however, since microbiological testing was not performed on day 55, it is recommended that the preparation be stored for no longer than 30 days.

The stability of tacrolimus in an extemporaneously compounded oral liquid formulation was studied. A suspension was prepared by mixing the contents of commercially available 5-mg capsules of tacrolimus with equal amounts of Ora-Plus and Simple Syrup, NF, to make a final volume of 60 mL. The final concentration of tacrolimus in the suspension was 0.5 mg/mL. Six identical suspensions were prepared, placed in three glass and three plastic amber prescription bottles, and stored at room temperature (24-26 degrees C). Immediately after preparation and at 7, 15, 30, 45, and 56 days, samples were removed and assayed in duplicate by stability-indicating high-performance liquid chromatography. At least 98% of the initial tacrolimus concentrations remained in all suspensions throughout the study period. Color, order, and pH did not change appreciably over the study period. Tacrolimus 0.5 mg/mL compounded extemporaneously in equal amounts of Ora-Plus and Simple Syrup, NF, was stable at 24-26 degrees C for at least 56 days in both glass and plastic amber prescription bottles.

The stability of itraconazole in an extemporaneously compounded oral liquid formulation was studied. A suspension was prepared from the beads contained in commercially available 100-mg itraconazole capsules and sufficient Simple Syrup, NF, to make a final volume of 60 mL. The final concentration of itraconazole in the suspension was 40 mg/mL. Three identical volumes of each suspension were prepared and stored in 2-oz capped, amber glass prescription bottles and refrigerated at 4 degrees C (range, 2-6 degrees C). Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected and assayed in duplicate by high-performance liquid chromatography; the pH of the samples was also determined. On day 35, the mean +/- S.D. percentage of initial itraconazole concentration remaining in the three suspensions was 95.3 +/- 2.2%. The color, odor, and pH of the samples did not change appreciably over the study period. Itraconazole 40 mg/mL in an oral liquid compounded from simple syrup and beads from capsules, stored in amber glass bottles, was stable for 35 days at 4 degrees C.

Objective: To determine the stability of cisapride in a liquid dosage form stored in plastic bottles at 2 temperatures. Design: Cisapride tablets were used to prepare a suspension in equal volumes of methylcellulose 1% and simple syrup to yield a concentration of 1 mg/mL. The cisapride suspension was stored in 10 amber plastic prescription bottles. Five bottles were stored at room temperature (25 ± 0.1 °C) and 5 under refrigeration (4 °C). Samples were drawn from each bottle immediately after mixing (day 0), and at 7, 14, 28, 42, 56, 70, and 91 days of storage at each temperature. All samples were analyzed in duplicate on each day of analysis. Cisapride was measured by a stability-indicating HPLC method. Results: The mean concentration of cisapride exceeded 90% of its initial concentration throughout the 91-day study period at 4 °C, but only during the first 28 days at 25 °C. No significant change in pH was observed during the study period. Conclusions: Cisapride was stable in a suspension for 91 days at 4 °C and 28 days at 25 °C in amber plastic prescription bottles.

The concentration uniformity of an extemporaneously prepared ranitidine suspension was studied. To prepare the ranitidine suspension, 36 150-mg tablets were pulverized and suspended in 180 mL of distilled water. This mixture was diluted with simple syrup to a total volume of 360 mL, resulting in a final ranitidine concentration of 150 mg/10 mL. Samples from each of three bottles that had been filled with 60 mL of the suspension were assayed for ranitidine content by high-performance liquid chromatography. The sedimentation of suspended ranitidine tablet particles was studied by visual observation of the setting process in 10-mL samples from the same batch. The overall mean concentrations (in milligrams per milliliter) of ranitidine were 14.53, 15.25, 13.92, 12.67, and 12.72 at 0, 3, 7, 14, and 21 days, respectively. Compared with baseline, the difference in the ranitidine concentration was not significant over days 0-7. The ranitidine concentration was significantly reduced during the following time intervals: days 0-14, days 0-21, and days 7-21. In the settling experiments, the mean time (+/- S.D.) for sediment to first appear on the test tube bottom was 14.67 +/- 5.35 seconds. Approximately 40-50% (mean level = 3.2 mm) of the total sedimentation level (mean level = 7.3 mm) was observed one minute after shaking. The uniformity of ranitidine suspensions compounded according to procedures described in this report possibly could be improved with sonication. The ranitidine suspension should be well shaken, the dosage should be measured immediately after shaking, and the suspension should be used within seven days of compounding.

Stability-indicating assay methods for the quantitation of hydralazine hydrochloride based on high-performance liquid chroma-tography using two different columns have been developed. Phenyl-prooanolamine can be used as an internal standard with both columns (μC18 and μphenyl) while hydrochlorothiazide can be used only with μphenyl column. The method is accurate and precise with percent relative standard deviations based on 6 readings of less than 2. The excipients present in the dosage forms did not interfere with the assay method. In combination with hydrochlorothiazide, hydralazine can be quantified only with μphenyl column. Two oral liquid dosage forms prepared in a local hospital using commercially available strawberry syrup/simple syrup decomposed completely in one day.

The stability of methyldopa in two extemporaneous syrup preparations was studied. Film-coated methyldopa tablets were triturated and incorporated into (1) unpreserved Syrup USP and (2) an equal mixture of simple syrup containing 0.5% citric acid and 0.2 N hydrochloric acid, in concentrations of 50 mg/ml. The preparations were stored in the dark, for 14 days at 5 C and 25 C. Samples were analyzed spectrophotometrically for methyldopa content at various intervals. Both preparations were stable under the conditions studied.

The effect of simple syrup dilution in Berotec ® Syrup with other liquids was investigated with regard to changes in appearance and pH value. These changes were tested immediatly and 3 and 7 days after admixing at 30°C and 5°C. The decrease of redistribution occured in admixture with Pontal® Syrup and Asverin® Syrup. A cotton-like substance was observed in all cases of admixtures tested within 7 days at 30°C and identified by IR Spectrum UV Spectrum and high-performance liquid chromatography as Hydroxypropylmethylcellulose (HPMC) which was the additive in Berotec® Syrup.

The design and construction of a laboratory size dryer and other accessories suitable for investigating the drying rate kinetics of granules under controlled external conditions are described. Granulations of lactose and sulfathiazole, representing water‐soluble and insoluble materials, were prepared using various commonly used binders, and their drying rates were determined. The binders and diluents affected the drying rate curves for these granulations both qualitatively and quantitatively. Granules made with starch paste and gelatin solution required maximum time and energy for drying and those made with simple syrup USP required the least among the binders studied. Generally, three linear slopes were observed when the drying rate was plotted against the moisture remaining, indicating that granulation drying may be considered as occurring through three distinct phases.

The stability of carbamazepine in four suspending vehicles is reported. Suspensions of carbamazepine 200 mg/5 ml in sorbitol 70%, simple syrup, modified Hospital of the University of Pennsylvania Suspending Vehicle (HUP), and diluted HUP (HUP-A) were prepared. The first three suspensions were stored in amber glass bottles and oral syringes at 4, 25, and 37 degrees C, and the HUP-A suspension was stored at 4 degrees C. Physical stability was assessed by visual inspection of sedimentation, ease of pouring, and foaming upon shaking. Carbamazepine concentrations were determined periodically over 90 days by an enzyme-multiplied immunoassay. The assay was validated by acid-heat degradation of the drug, separation of breakdown products by thin-layer chromatography, and confirmation of non-reactivity of the breakdown products with the assay. The concentration of carbamazepine in sorbitol 70%, simple syrup, and HUP-A was at least 90% of the prepared concentration at all sampling times. Although separation occurred, the simple syrup suspensions could be redispersed. The suspension in HUP-A remained homogeneous, was easy to pour, and produced less foam than the HUP suspension. Extemporaneously compounded suspensions of carbamazepine in HUP-A or in simple syrup can be used for patients who require a liquid dosage form. Even though sorbitol 70% produced a pharmaceutically acceptable product, its use is not recommended because it has been reported to cause intractable diarrhea.

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

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Background: Most medicines are available only as solid, adult-strength dosage forms from which oral extemporaneous liquids are often prepared for children. There are few comprehensive reference lists for the preparation of pediatric extemporaneous formulations. Some pediatric reformulations are made by diluting the suspending vehicle, and a shelf life of up to 3 months can be used without documented microbial stability. Although most commercially available ready-to-use vehicles are supplied as preserved formulations, it is still common practice in many European dispensaries to prepare and dilute these vehicles as required for specific prescriptions. Objective: To determine what influence dilution of vehicles has on the preservation efficiency of extemporaneous formulations. Methods: Suspending vehicles were made by diluting methylcellulose 1% and simple syrup, BP (British Pharmacopoeia) in ratios of 1:1 and 1:4. The efficacy of antimicrobial preservation was tested according to the 2007 standards required by the BP. Results: Dilution in ratios greater than 1:1 failed the BP 2007 criteria. Such dilution represents a potential biohazard, especially to premature, newborn, or immunocompromised children, exposing them not only to possible organoleptic changes of the preparation, but also to ingestion of either dangerous numbers of microorganisms or medicines that may have undergone biotransformation, rendering them inactive or toxic. Conclusions: Significant concerns have been raised regarding the quality of extemporaneous preparations. We call for further research in this neglected area to address issues of antimicrobial preservation, including revision of existing quality assurance monographs. Moreover, these monographs should take into account testing that simulates multiple dosing from a single storage container during the intended in-use shelf life of multidose extemporaneous preparations.