Search

Background: Clofazimine is recommended as a treatment for tuberculosis in infants. Extemporaneously prepared clofazimine oral suspensions are more appropriate dosage forms for infants than tablets, however no data exist to inform appropriate storage conditions. Aim: To examine the physical and chemical stability of extemporaneously prepared clofazimine oral suspensions and determine appropriate storage conditions. Method: An oral suspension of clofazimine 10 mg/mL was prepared by grinding six 100 mg clofazimine tablets to produce a fine powder. Ora‐Blend SF (sugar free) was added to make a final volume of 60 mL. Six 10 mL aliquots were placed in amber plastic bottles with plastic bottle caps. Three bottles were stored at room temperature, and three bottles were refrigerated at 4°C. Following shaking, a 1 mL sample was taken from each bottle on days 0, 7, 14, 28, and 60. Samples were assayed using the high‐performance liquid chromatography method. The samples were visually examined for colour change and separation at each time point. Stability was defined as the retention of at least 90% of the initial concentration. Ethics approval was not required for this research article as it was a stability study that did not involve human subjects. Results: The clofazimine content remained >94% of the initial concentration throughout the 60‐day period for samples that were kept at room temperature, and slightly <90% (87.4%) for samples that were kept refrigerated at 4°C. No separation or colour change was noted throughout the 60‐day period for both preparations. Conclusion: Extemporaneously prepared suspensions of clofazimine in Ora‐Blend SF were chemically stable for at least 60 days when stored at room temperature. Clofazimine degraded slightly more rapidly at 4°C compared to room temperature. [ABSTRACT FROM AUTHOR]

Stability assessments are crucial in determining the shelf-life and quality of compounded pharmaceutical products. Folic acid, an essential B-vitamin, is widely used to prevent and treat folate deficiency-related conditions. However, because of patient-specific demands or customised dose requirements, compounded folic acid syrups are frequently used in pediatric patients. This study aims to examine the stability of compounded folic acid mixtures prepared with some commercially available vitamin syrups. Three commercially available vitamin syrups were utilized as compounding vehicles for folic acid tablets, ensuring a representative sample of products commonly used in compounding practices in hospitals when conventional compounding vehicles are not available. The compounded folic acid mixtures were stored under ambient (21-25 ℃) and refrigerated conditions (2-8 ℃), to simulate real-life scenarios, and tested using parameters such as, organoleptic characteristics, sedimentation rate, pH, microbial growth and drug content determination at day 7, 14 and 30. The extemporaneous preparations of the compounded folic acid in vitamin syrups generally maintained their physical characteristics over the 30-day study period. However, there was either decrease in folic acid concentration or microbial contamination of the preparations at day 7. Therefore, folic acid compounded in vitamin syrups are generally stable for less than seven days. The data obtained will aid healthcare professionals and compounding pharmacies in decision making concerning the choice of vehicle, compounding practices and strategies to ensure the preparation of wholesome extemporaneous products. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of the study are to develop and validate a stability-indicating method for evaluating the stability of extemporaneous oral liquid formulations containing 50 mg/mL isoniazid (INH) prepared from INH drug substances and INH tablets. Materials and Methods: The optimized high-performance liquid chromatography (HPLC) conditions included a C18 column (250 mm × 4.6 mm, 5 µm), a flow rate of 1 mL/min, a column temperature of 30°C, and a detection wavelength of 254 nm. The separations were performed using a gradient HPLC system, employing acetonitrile and water as the mobile phases. The method was validated according to ICH Q2(R1) guidelines. The validated method was applied to assess the INH concentration in extemporaneous oral liquid preparations stored under refrigerated conditions (4 ± 2°C) for duration of 180 days. Results: The optimized method enabled the simultaneous determination of INH and its degradation products in lactose-containing samples. The peak purity index of INH was 1.0000. The linearity assessment over a concentration range of 10-150 µg/mL yielded correlation coefficients (r) surpassing 0.999. Accuracy was observed within the range of 99.24%-100.53%, and the relative standard deviations for intra-day and inter-day precision remained below 1.0%. The investigated formulations contained >93% of the labeled amount of INH throughout the study period, indicating acceptable stability. In addition, no significant changes in pH or color were detected. It was also discovered that the examined commercially available INH tablets are lactose-free formulas. Conclusion: The study reveals that the use of INH substances and lactose-free tablets for oral liquid formulations results in a prolonged stability period than indicated by previous research. This study not only contributes to the validation of a reliable stability-indicating method but it also provides stability data for an extended shelf life of the extemporaneous INH oral liquids, which can improve patient convenience and consequently patient compliance. [ABSTRACT FROM AUTHOR]

Cryptosporidiosis is an infectious disease caused by the Cryptosporidium parasite, primarily affecting the gastrointestinal tract of both humans and animals. Transmission occurs via fecal-oral route, mainly through ingestion of water or food contaminated with oocysts, the parasite’s infectious form. Immunocompromised individuals are particularly susceptible to severe and prolonged symptoms. Current treatment strategies involve supportive measures and antiparasitic medications such as nitazoxanide and paromomycin, although patients with predisposing factors have an elevated risk of recurrence. There is currently no evidence supporting the use of paromomycin via nasogastric tube. Therefore, we present our experience with the use of an extemporaneous paromomycin solution and its clinical impact. [ABSTRACT FROM AUTHOR]

Cancer treatment is evolving. Oral formulations offer potentially more convenient, effective alternatives to conventional chemotherapy for many cancers. An appealing aspect of oral antineoplastic agents is their relative ease of administration; unfortunately, patients may have difficulty swallowing the tablets or capsules. This shift towards oral administration and the accompanying issues around oral medication adherence highlights the need to assess the safety and feasibility of delivery methods for patients unable to swallow solid dosage forms. A new medication‐use process (MUP) was created to facilitate extemporaneous compounding of oral oncology drugs (OOD). Systematic review consisting of tertiary resources, drug manufacturers, and primary literature was performed to identify information related to extemporaneous compounding or alternative routes of administration for a predetermined list of OODs. A single‐center retrospective review was conducted of patients receiving liquid formulations of OODs to characterize institutional experience. Overall, 116 OODs were reviewed. The majority of OODs had information describing extemporaneous compounding or alternative routes of administration (31% with commercial liquid formulations available or information in tertiary resources; 33% with off‐label manufacturer information or case reports) while 36% had no data. The MUP included three compounding workflows to account for available solid dosage formulations (tablet, hard capsule, gelatin capsule) and creation of an electronic health record order template. Retrospective review identified 41 patients who received compounded liquid formulations of 14 OODs for 13 indications. Liquid OODs were used for a median of 3‐5 days. None of the 41 patients experienced discernable safety or overt effectiveness concerns readily attributed to use of liquid OODs. Implementation of a novel MUP and systematic review of OODs aids the pharmacist in standardizing institutional practice and mitigates risks associated with extemporaneous liquid formulations of OODs facilitating medication delivery of new agents to patients unable to swallow solid dosage forms. [ABSTRACT FROM AUTHOR]

Purpose: Research has shown that co-administration of preparations containing HQ and azelaic acid (AZ) or vitamin C (vit C) may be more effective than HQ alone. The aim of this study was to evaluate the stability of HQ in the presence of AZ and vit C as active ingredients in the extemporaneous preparations prepared with different techniques. Methods: Topical preparations containing HQ, vit C, and AZ were prepared using with aqueous and none-aqueous extemporaneous techniques. Some auxiliary antioxidants were used to stabilize vit C. Thermal stress condition was applied for stability evaluation. Digital images and HPLC analysis were performed to control the color changes and drug loss, respectively. Results: Severe color changes happened in some formulations and dark brown color appeared. Color change was directly attributed to vit C loss but not related to HQ loss. HQ ointment with no antioxidant, showed no loss after stress incubation. AZ was partially able to increase the HQ and vit C stability in a combination formulation, but this stabilizing effect in binary formulations of HQ and AZ was not seen. SMB enhanced vit C stability. Aqueous preparation methods decreased the stability of formulations significantly. It can be recommended that HQ, vit C, and AZ be formulated in separate dosage forms. Conclusion: Avoiding water incorporating or aqueous methods will enhance the stability of these formulations, as well. Intrinsic low stability of vit C in topical formulations may be enhanced using non-water incorporating or non-aqueous methods and utilizing SMB in suitable concentrations. [ABSTRACT FROM AUTHOR]

Background: Many studies have demonstrated the effectiveness of hydroxyurea in the management of sickle cell disease. The drug, which is an antimetabolite initially developed for the treatment of myeloproliferative disorders has been repurposed, even though its use for the initial indication has been retained. Currently, in most developing countries the only available dosage form is the 500 mg capsule. Pediatric hydroxyurea formulations are yet to appear on many markets, thus, patients have to rely on compounding facilities to have their medications extemporaneously prepared for them from the adult solid dosage form. Interestingly, pharmacies that provide compounding services are limited, additionally; most extemporaneously compounded products have very short shelf lives. The aim of this study was to formulate and optimize dry powder granules of hydroxyurea to be reconstituted into an oral suspension in order to prolong the shelf life of the product. Method: Two different batches of Hydroxyurea granules were formulated using the wet granulation method. Granules were characterized by appearance, pH and drug content. Microbial contamination test was conducted using the pour plate method. Results: Granules prepared were easy to reconstitute. pH of the suspensions were between 7 and 8. Drug content in formulated granules were 95 and 92% of expected values. No E. coli was found in the suspensions and the total microbial count was less than the USP limits. Granules remained stable over the study period of 60 days. Conclusion: Dry granules of hydroxyurea can be produced in bulk and packaged into bottles for reconstitution into suspensions by patients. These formulations have better stability than extemporaneously compounded suspensions. Making hydroxyurea granules available for children with sickle cell disease will be a convenient, time and cost effective way of meeting their medical needs.

Muluken Nigatu Selam,1 Andualem Ababu2 1Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Pharmaceutical and Medical Equipment Directorate (PMED), Ministry of Health, Addis Ababa, EthiopiaCorrespondence: Muluken Nigatu SelamDepartment of Pharmaceutics and Social Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O. Box 1176, Addis Ababa, EthiopiaTel +251912159807Email muluken.nigatu@aau.edu.etAbstract: Extemporaneous compounding is among the key hospital pharmacy services that promotes pharmaceutical care. It is a long-standing practice in dermatology for patients who need custom-made drug products. The practice of dermatologic compounding practice in Ethiopian public hospitals is found at the beginning and very few hospitals have started the practice so far. This research communication aimed at examining Ethiopian public hospitals’ extemporaneous compounding practice for dermatologicals with emphasis on regulatory requirement and quality control activities. To benefit patients from these products, good compounding practice should be obeyed in line with the expansion of the service. Gaps have been observed in the facilities with regard to quality assurance system and compliance with the country’s regulatory requirements. This implies a need to take appropriate and timely actions by the responsible stakeholders and expand the service in the country by fulfilling the regulatory requirement.Keywords: compounding, dermatologic, extemporaneous, regulatory, quality, hospitals

The lack of appropriate medicines for children has a significant impact on health care practices in various countries around the world, including Thailand. The unavailability of pediatric medicines in hospital formularies causes issues regarding off-label use and extemporaneous preparation, resulting in safety and quality risks relating to the use of medicines among children. This research aimed to identify missing pediatric formulations based on the experience of healthcare professionals in a teaching hospital in northern Thailand. A cross-sectional survey was conducted to collect data on missing pediatric formulations, the reasons for their inaccessibility, their off-label uses, their reactions to the situation, and suggestions to improve access to these identified medications. The survey was distributed to all physicians, nurses, and pharmacists involved in prescribing, preparing, dispensing, and administering pediatric medicines. A total of 218 subjects responded to the survey. Omeprazole, sildenafil, and spironolactone suspension were most often identified as missing formulations for children by physicians and pharmacists. They are unavailable on the Thai market or in any hospital formulary. For nurses, sodium bicarbonate, potassium chloride, and chloral hydrate were the most problematic formulations in terms of preparation, acceptability, and administration. These medicines were difficult to swallow because of their taste or texture. [ABSTRACT FROM AUTHOR]

Introduction: Rifampicin is a first line antituberculosis drug that is commonly used in the treatment of tuberculosis, both in adults and paediatric patients. However, there is a lack of liquid formulation for rifampicin in the market due to the small market size and the physicochemical properties of the drug itself. An innovative new mix called X-Temp® oral suspension system (OSS) has been available in the market as a choice of vehicle for extemporaneous suspension. Aim: The aim of this study was to prepare rifampicin suspension in the X-Temp® OSS and evaluate its stability following storage at two temperatures – refrigerated (5 °C ± 3 °C) and in a stability chamber (30 °C ± 2 °C/RH 75% ± 5%). Materials and method: This study investigates the physicochemical and microbiological stability of rifampicin formulated in X-temp® OSS. The rifampicin suspension was prepared at 25mg/ml and kept in two types of amber-coloured storage bottles. The bottles were stored in an open and close storage system at 5 oC (refrigeration) and 30 °C/75% RH (non-refrigerated) and the stability of the product was evaluated at specified time intervals. Results: It was found that the content of rifampicin remained above 90% of the original concentration throughout the study as required by the standard references. Visual appearance, colour, odour and pH remained unchanged throughout the study period and the extemporaneous preparation was not susceptible to microbial contamination. Conclusion: Results from this stability study confirmed that the X-temp® OSS is a suitable vehicle for the preparation of extemporaneous rifampicin liquid formulation.

Parotid gland tumor is complex and poses diagnostic and therapeutic problems. The purpose of this study was to assess the role of extemporaneous examination in the management of patients with parotid gland tumors. We report a pro and retrospective analytical study of a series of cases of salivary gland tumors, whose data were collected in the ENT and in the department of cervical-facial Surgery at the University Hospital in Casablanca, between January 2012 and December 2015. Seventy two cases of parotid tumors were recorded. The sex-ratio (H/F) was 0.94, 0.76 for patients with benign tumors and 1.62 for patients with malignant tumors. The average age was 47 years (15- 75 years). The median of consultation time was 40 months. Clinical symptoms were dominated by parotid swelling (100%), pain in 25% of patients, facial palsy in 6%, and cervical adenopathies in 10%. Ultrasound was recommended in 80% of patients. MRI was performed in 26% of cases. All patients underwent surgery, 76% of patients underwent exofacial parotidectomies and 24% total conservative parotidectomies. This treatment was associated with ganglion resection in 24% of cases and radiotherapy in 24% of cases. Extemporaneous examination was performed in 71% of patients, its susceptibility was 89% and its specificity 88%. Definitive histological diagnosis was confirmed by anatomopathological examination in all cases. We confirmed benign and malignant tumors in 71% and 29% of cases respectively. Benign tumors were dominated by pleomorphic adenoma (59%), while malignant lesions were dominated by mucoepidermoid carcinoma (38%). The postoperative course was marked by: discrete haematoma in 4% of cases, transient facial palsy in 15%, superinfection of the wound in 3% and post- parotidectomy Frey's syndrome in 3% of patients. One patient had labial recurrence of acinar cell carcinoma. No cases of death were noted. Parotid gland tumors are characterized by a great histological variability. Differentiation between malignant tumor and benign tumor is often difficult. Currently, MRI is the imaging test of choice. Extemporaneous examinationis is very useful intraoperatively when it is necessary to communicate with the pathologist. Multidisciplinary approach is adopted including ENT, oncological, radiotherapeutic, pathological and radiological approaches. Prognosis depends on the histological type, the stage of progression and treatment. [ABSTRACT FROM AUTHOR]

Objectives: 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.Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objectives: It has been shown that nifedipine cream 0.5% is effective in the treatment of anal fissure and in reducing facial wrinkles. However, no commercially manufactured formulation of this product is available in some countries and prescriptions for the medication need to be extemporaneously compounded by retail pharmacies. So, the aim of this study was to evaluate the quality of the compounded nifedipine cream 0.5%. Methods: Twenty‐one compounding pharmacies within Tehran area were randomly included in this study. A physician wrote the prescriptions for compounded nifedipine in dexpanthenol cream (0.5%) for fictitious patients, with two refills allowed per prescription. The extemporaneous products were analysed for potency and microbial limit using validated methods. Key findings: There was a significant variability both within and between pharmacies with respect to the potency of the compounded products. By contrast, no microbial contamination was detected in these products. Of 63 prescriptions, nifedipine concentration of 21 products (33.33%) was within ±20% of the prescribed dose. Thirty‐ nine (61.90%) were sub‐potent, which ranged in potency from 24.33–77.57%. One pharmacy provided products with essentially no nifedipine. Conclusion: Compounded nifedipine obtained from pharmacies in this study did not raise safety concerns when assessed for microbial contamination. However, compounded products may be misbranded, which may negatively impact the management of anal fissure and facial wrinkles. [ABSTRACT FROM AUTHOR]

Great impromptu speaking, reciting and singing are never just an isolated impromptu act. It is the result of endless practice to perfect performance that can then be given impromptu. One of the main objectives of learning English as a Second Language (ESL) is to be able to speak English impromptu, not just on the stage or in front of an audience but also in a casual meeting, on the street or during a formal meeting in a board-room. In fact to be able to speak “impromptu” should be the Holy Grail of teaching and learning ESL, more important than reading, writing and listening. So how come it is not given the priority it deserves – and how come it seems such a difficult goal? We believe it is because teachers and learners neglect to emphasize and practice the key to learning impromptu speaking. That key we believe is practice, practice and more practice. We can remember songs from our kindergarten years and we can still sing them because we practiced, practiced and practiced them. We believe that the teaching of ESL often overlooks the critical importance of lots of practice to create depth of learning and that creative methods of practicing need to be taught and practiced in ESL courses until such methods become deeply habitual, in fact they become a new personal paradigm. If our students aim to become great at ESL, they, too, must take continuous never-ending practice to heart.

Purpose. The stability of an extemporaneously prepared rosuvastatin suspension stored over 30 days under various storage conditions was evaluated. Methods. Rosuvastatin suspension was extemporaneously prepared using commercial rosuvastatin tablets as the source of active pharmaceutical ingredient. The organoleptic properties, dissolution profile, and stability of the formulation were investigated. For the stability studies, samples of the suspension were stored under 2 storage conditions, room temperature (25 °C and 60% relative humidity) and accelerated stability chambers (40 °C and 75% relative humidity). Viscosity, pH, organoleptic properties, and microbial contamination were evaluated according to the approved specifications. High-performance liquid chromatography was used for the analysis and quantification of rosuvastatin in selected samples. Microbiological investigations were also conducted. Results. The prepared suspension showed acceptable organoleptic properties. It showed complete release of rosuvastatin within 15 minutes. The pH of the suspension was 9.8, which remained unchanged during the stability studies. The microbiological investigations demonstrated that the preparation was free of any microbial contamination. In addition, the suspension showed stability within at least the period of use of a 100-mL rosuvastatin bottle. Conclusion. Extemporaneously prepared rosuvastatin 20-mg/mL suspension was stable for 30 days when stored at room temperature. [ABSTRACT FROM AUTHOR]

Abstract: There is some confusion about the types of paediatric pharmaceutical preparation (in a regulatory and pharmaceutical development context) that are acceptable for approval by medicines regulators. Some of the confusion relates to terminology which may mean different things to different stakeholders. It may not always be possible to provide authorised, commercially manufactured, age appropriate, ready-to-administer preparations. In terms of assurance of quality and bioavailability there is a continuum from this ideal through intermediate products through authorised compounding and manipulation of commercial dosage forms to ad hoc compounding using only the skills and experience of the individual pharmacist. Additionally, it is widely known that caregivers may manipulate medicines at home, for example by segmenting tablets and by addition to foods or liquids. The first intent of the manufacturer should be to provide for children an age appropriate, ready-to-administer preparation which is commercially manufactured and approved by the competent authorities. However, there will still be a place for providing other age appropriate preparations such as approved products that are ‘intermediates’ requiring reconstitution before use, or instructions for compounding or manipulation of a dosage form. If compounding or manipulation is likely to be required it is preferable that data are generated by Industry, approved by the competent authorities and provided in the Summary of Product Characteristics (SmPC). It is acknowledged however, that ad hoc compounding or manipulation may also take place in certain circumstances such as logistical difficulties or to satisfy the needs of the child who does not find the authorised product to be ‘age appropriate’. This paper explores compounding and manipulation of medicines in relation to approval by medicines regulators and non-approved preparation to fulfil the needs of the individual patient. Definitions are proposed to provide a hierarchical classification based on assurances of quality and bioavailability. [Copyright &y& Elsevier]

im of the Review Extemporaneous compounding has been a core function for pharmacists and was the basis of pharmacy's claim to professional status. The re-emergence of compounding as a specialised practice warrants investigation regarding the influence of this practice on pharmacy's professional status. The aim of this study was to investigate the contribution of extemporaneous compounding to the professional status of pharmacists in community practice. Method A search of the literature was conducted using MEDLINE, EMBASE, IPA, ISI WEB OF KNOWLEDGE, PROQUEST SOCIAL SCIENCE JOURNALS, JSTOR and SOCIOLOGICAL ABSTRACTS databases to identify relevant original research articles, reviews or commentaries. Results Compounding was an important part of pharmacy's claim to professional status. The expansion of the pharmaceutical industry and decline in demand for compounded medications led to a view that pharmacy suffered a loss of professional status. In recent decades patient centred services have been introduced as a reprofessionalisation strategy. Evidence suggests that compounding, as a specialty practice based on a patient centred approach, is increasingly provided in Australia and the United States. Conclusion Compounding has emerged as a specialised area of pharmacy practice in Australia and the United States, and when practiced as a patient centred activity may be a strategy for reprofessionalisation. The extension of compounding beyond mere supply and distribution of a pharmaceutical product to become a platform for development of collaborative professional relationships may also lead to enhanced professional status of pharmacists. [ABSTRACT FROM AUTHOR]

Oncology pharmacists face a constant challenge with patients who cannot swallow oral anticancer drugs, making extemporaneous oral liquid preparation a requirement. Improper extemporaneous preparation of these agents, especially with the traditional chemotherapy with a narrow therapeutic index, may increase the risk of over- or underdosing. In community pharmacies, multiple barriers exist that prevent these pharmacies from preparing extemporaneous oral anticancer drug formulations for a patient's use at home. In a home setting, patients or caregivers without proper counseling and education on how to safely handle chemotherapy are at increased risk for exposure to these drugs. Based on a review of the literature, compounding recipes are available for 46% of oral anticancer agents. A paucity of data exists on dose uniformity, bioequivalence, and stability of extemporaneous oral liquid formulations of anticancer drugs. Pharmacists must have an understanding of the basic scientific principles that are an essential foundation for the proper preparation of extemporaneous oral anticancer liquid formulations. The collaborative effort of a multidisciplinar team can also help identify different barriers in the community setting especially in areas where community pharmacies may lack resources for the extemporaneous compounding of oral chemotherapy, and to find ways to coordinate better pharmaceutical care. There are great opportunities for oncology pharmacists, as well as community pharmacists, as a resource for educating and monitoring patients receiving oral chemotherapy to ensure dosing accuracy, safe administration, and proper disposal of hazardous drugs. Development of national guidelines to promote standards of practice in the community and/or home setting is urgently needed to help improve the safety of dispensing and handling oral chemotherapeutic agents, including extemporaneously compounded oral liquid formulations of these drugs. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Pediatric Formulation Initiative (PFI) is a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The PFI was established to address the issue of the lack of appropriate formulations in children and to use this activity as a means to improve pediatric formulations, as mandated by the Best Pharmaceuticals for Children Act of 2002 and 2007. The PFI began in 2005 with the formation of 3 working groups—Scientific, Economics, and Taste and Flavor. These groups began the process of identifying issues, gathering needed information, and considering possible ways to overcome barriers to the development of pediatric drug formulations. Objective: The purpose of this supplement was to provide details of the working groups'' activities through presentation of full-length articles. Also presented is an article that discusses the 2007 European Union (EU) regulation on medicinal products for pediatric use. Methods: Information for this article was gathered from the proceedings of a PFI workshop, sponsored by the NICHD, that was held in Bethesda, Maryland, on December 6 and 7, 2005, as well as postworkshop discussions of the different working groups. Results: The increased awareness that the majority of medications used today have not been labeled for use in children, and have not been tested to define safety, efficacy, and appropriate dosing, has led to the passage of legislation in the United States and in the EU to create incentives to stimulate the testing of drugs in this special population. It is imperative that the problems associated with the compounding and use of extemporaneous formulations as described in this supplement be addressed. Regulatory barriers to the availability of commercially developed pediatric formulations in different countries will need to be minimized or removed. New drug delivery systems will need to be tested and made available to pediatric patients. Further research in the mediators of bitter taste and study of taste blockers, as well as newer methods for taste testing in pediatrics, should be encouraged. An overarching goal for the future is addressing the economic barriers to develop appropriate pediatric dosage forms for drugs with limited market penetration. The lack of appropriate formulations is part of a larger problem that includes limited development and manufacture of medicines tailored for pediatric patients (particularly those affected by neglected diseases), insufficient investment in drug trials, and limited research on drug disposition in various pediatric populations worldwide. Conclusion: The solution to these issues will require alignment of vision and commitment as a global priority of policy makers, regulators, scientists, pharmaceutical sponsors, academic institutions, governments, and research foundations. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective. – Preliminary assessment of a rotary thromboelastometer (Rotem™) in the haemostasis monitoring in ICU. Study design. – Prospective, open. Patients and methods. – The device: the Rotem™ is a rotary thromboelastometer, which measures continuously and retranscribes numerically viscoelastic properties of a clot after an in vitro haemostasis activation. 83 patients with various haemostasis disorders that 122 blood samples have been subjected to a double analysis: extemporaneous by Rotem™ and at the laboratory for conventional haemostasis tests (aPTT, PT, fibrinogen, platelets). We assessed Rotem™''s manipulation duration, time for the first results. We compared Rotem™ variables with conventional haemostasis parameters and haemostasis diagnosis with each method. Results. – Mean Rotem™ manipulation duration was measured at 2 minutes 51 seconds±1 minute 48 seconds and time for results at 13±6 minutes. Plasma fibrinogen level was strongly correlated with the kinetic of clot formation (CFT) and the maximun clot firmness (MCF) measured by Rotem™ (R >0.7, coefficient of Pearson). Platelets were strongly correlated with MCF. The PT and aPTT had a weak correlation with Rotem™ parameters (R ≤0.53). The diagnosis concordance between the two techniques was good with a pondered κ coefficient measured at 0.68. Hypocoagulability thromboelastographic profile with Rotem™ was in agreement with conventional parameters diagnosis in 92 percent of cases. Hypercoagulability thromboelastographic profile was associated with a significant increase of conventional parameters (supranormal value in 78%). Normal thromboelastography profile was associated with normal conventional parameters in 49%. Different reagents used on several simultaneous tests specified the thromboelastographic diagnosis. A diagnostic algorithm showed the interest of the Rotem™ for the prediction of conventional test results. Conclusion. – Rotem™ is an easy manipulation device whose concordant and rapid results allow its emergency use in the framework of haemorrhagic situations. It also allows an approach of hypercoagulability states so that the therapeutic implication remains to evaluate. The Rotem™ offers a dynamic multifactorial approach on total blood of haemostasis that is what makes it a prime aid of haemostasis monitoring, in complement of usual analytic haemostasis evaluation. [Copyright &y& Elsevier]

Abstract: The purpose of the research described herein was to develop and validate a stability-indicating HPLC method for lisinopril, lisinopril degradation product (DKP), methyl paraben and propyl paraben in a lisinopril extemporaneous formulation. The method developed in this report is selective for the components listed above, in the presence of the complex and chromatographically rich matrix presented by the Bicitra® and Ora-Sweet SF™ formulation diluents. The method was also shown to have adequate sensitivity with a detection limit of 0.0075μg/mL (0.03% of lisinopril method concentration). The validation elements investigated showed that the method has acceptable specificity, recovery, linearity, solution stability, and method precision. Acceptable robustness indicates that the assay method remains unaffected by small but deliberate variations, which are described in ICH Q2A and Q2B guidelines. [Copyright &y& Elsevier]

Background: Olmesartan medoxomil (OLM) is only available in the United States as tablets. The United States Pharmacopoeia (USP) has placed OLM on its priority list of preparations that require stability data to support practitioner compounding. Objective: The purpose of the study was to develop a stability-indicating assay and then determine the beyond-use date (BUD) for an extemporaneous OLM suspension. Methods: A reverse-phase high-performance liquid chromatography (HPLC) assay was developed and validated according to guidelines for USP official compounded monographs. OLM 2 mg/mL suspensions were compounded with Ora-Sweet and Ora-Plus and stored at room temperature or in a refrigerator. Suspensions were assayed periodically over 90 days for OLM concentration and observed for physical stability. The pH was measured at the beginning and end of the study. Results: The OLM concentration remained above 97% of the starting concentration for 90 days when stored in the refrigerator and above 94% of the starting concentration for 90 days when stored at room temperature. The suspension pH did not change and indicators of physical stability were unchanged for 90 days. Conclusion: OLM 2 mg/mL suspensions were chemically and physically stable at room temperature and in the refrigerator for 90 days. The BUD may be set at 90 days under either storage condition., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objectives: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2019 John Wiley & Sons Ltd.)

Background: Statins are the first-line therapy for lowering high lipid levels. Atorvastatin calcium (AtC) is the most commonly prescribed statin. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which converts HMG-CoA into mevalonic acid, a cholesterol precursor., Objective: To compound and evaluate the stability of AtC suspension (0.4% w/v) using commercial tablets or pure AtC powder as the source of the active pharmaceutical ingredient., Method: Several AtC suspension formulations were produced using commercial AtC tablets or AtC pure powder as the source of the active ingredient. The most suitable one in terms of general organoleptic properties and dissolution was selected for stability studies. For this purpose, samples of final suspensions were stored at room temperature and in the refrigerator. Assay, pH, organoleptic properties and microbial contamination were evaluated according to the USP specifications. High performance liquid chromatography was used for the analysis and quantification of AtC in the studied samples., Results: The obtained suspension (S4) had good organoleptic properties. It showed complete dissolution of AtC within 30 min. However, the suspension prepared from crushed tablet (S t 4) showed a better dissolution profile than that prepared from pure powder (S p 4). The prepared formula had unchanged pH, which remained around 9.9. S t and S p formulas were both free from microbial contamination. Both products showed good stability within at least the period of use of the 100 mL AtC bottles., Conclusions: AtC extemporaneous suspension was successfully prepared using tablets as a source of AtC or pure AtC powder. However, S t 4 had a better dissolution profile than S p 4. This study provides a solution for patients with swallowing difficulties or feeding tubes who are unable to take medicines in solid oral dosage forms. Community pharmacists can prepare the suspension using AtC tablets as the source of the active ingredient., Competing Interests: Competing interests: None declared.

Background: Furuncular myiasis is a parasitic disease caused by the development of human botfly larva in the skin. It affects people living in tropical countries and travelers returning from these countries and concerns a number of medical specialties. One form of treatment involves surgical extraction of the parasites., Patients and Methods: We report the case of a 47-year-old man returning from Guyana presenting two furuncle-like nodules of the skin on the right buttock and on the right shoulder blade. Extemporaneous intraoperative macroscopic examination of the buttock nodule resulted in diagnosis of myiasis caused by the human botfly, Dermatobia hominis., Discussion: The diagnosis of furuncular myiasis is made primarily on clinical grounds and should be suspected on observation of an abscess in subjects returning from a tropical region. It is consequently rare to find D. hominis in biopsy specimens. In the present case, macroscopic examination showed an extremely rare image of the edge of the intact larva in a longitudinal cut, which to our knowledge has never been published to date., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Topical use of systemic agents to treat cutaneous disorders is widely applied. However, there is a lack of articles summarizing the relevant literature in a systematic way. Objective: We sought to review the published literature regarding topical use of systemic drugs that were categorized according to their mode of actions. Only drugs that are not yet commercially available in a topical preparation are included. Methods: A PubMed search was performed, using as key words “topical,” “extemporaneous,” “compounding,” and names of each generic drug, to identify all clinical reports (1966-2009). Results: Although many systemic drugs are used topically, randomized controlled trials were limited to a few agents. Limitation: Many of the reports consist only of small case series or are anecdotal in nature. As the level of evidence is limited, larger prospective trials are needed before firm conclusions can be drawn. Conclusion: Extemporaneous compounding helps physicians to individualize treatment to the patient’s specific needs and to create topical preparations that are not otherwise commercially available. However, comparative effectiveness studies are needed to determine whether or not topical use of systemic therapeutics is more beneficial than existing therapies. [Copyright &y& Elsevier]

Pharmaceutical preparations are medicines that the pharmacist makes for the special needs of the patients that the pharmaceutical industry cannot comply for economic and logistic reasons. Pharmacy compounding is still an important component of pharmacy practice and a valuable therapeutical service that is an integrant part of the modern health care system, but its legislation is not harmonized among European and US countries. In 2011 the Committee of Ministers of the Council of Europe has adopted a Resolution on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. Aim of this resolution is to harmonize quality assurance and standards for pharmacy-made medicinal products among European countries and to pass the gap in quality assurance and standards between preparation in pharmacies and medicines prepared by the pharmaceutical industry. This article will analyze the actual rules and technical norms that regulate compounding activity and the expectations resultants from the new European and US laws., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)