The stability of quetiapine oral suspension compounded from commercially available tablets

Quetiapine fumarate (QF) is an atypical antipsychotic used off-label for the treatment of delirium in critically-ill infants and children. For the treatment of pediatric populations or patient populations with trouble swallowing tablets, an oral suspension would be an ideal dosage formulation. However, there are no liquid formulations of QF commercially available. Therefore, a compounded oral suspension prepared from the commercial QF tablets is widely used in clinical settings. The extemporaneous preparation of QF compounded oral suspension changes the formulation from a solid form to a liquid form. Thus, the stability of QF compounded oral suspension should be critically evaluated to guide pharmacists for administration and storage of QF compounded oral suspensions. However, the stability of the nonaqueous oral QF suspension was not measured. The objective of this study was to develop QF compounded oral suspensions at 10 mg/mL by using commercial QF tablets in two readily available aqueous vehicles (Ora-Sweet and Ora-Blend) and measure their stability at both room temperature and under refrigeration. Physical stability of the QF compounded suspensions were evaluated by appearance and odor. Chemical stability of the QF compounded suspensions were evaluated based on pH, degradation, drug content and the amount of the drug dissolved in the vehicles. An HPLC method was validated and used to evaluate QF compounded suspensions over 60 days. In addition to the total drug in the suspensions, the dissolved drug in the vehicles was also measured during the stability testing and evaluated as a stability parameter. Overall, QF suspension prepared in Ora-Blend was preferable, demonstrating a superior 60-day stability at both room temperature and refrigerated storage.

Preparation and Evaluation of Extemporaneously Compounded Aspirin Capsules from Crushed Aspirin Tablets

Aims: Extemporaneous preparations of medications might bring about technical and clinical consequences due to formulation failures. Therefore, all such prepared formulas should undergo valid and reliable procedures supported by solid data. Otherwise, patients can experience significant risk due to microbial contamination or physical or chemical changes during the preparation process. Thus, effective extemporaneous preparation relies on correct calculations to avoid extra and serious harm. Therefore, because 50-mg aspirin capsules are not available in Saudi Arabia, this study aimed to formulate 50-mg capsules from available 100-mg aspirin tablets. Methodology: Quality control tests of the preparations were carried out at the time of preparation and after one month of storage at 25 °C and at 40 °C and 75% relative humidity. All tests were carried out according to the British and United States pharmacopeia monograph of aspirin. Results: The drug content assay and uniformity test indicated that the aspirin capsules were within the pharmacopeial limits. The disintegration time for all aspirin capsules was within the pharmacopeial limits of 30 minutes. The aspirin release profile showed that approximately 90% of the aspirin dissolved after 10 minutes. Conclusion: The results indicated that the extemporaneous preparation of ASA capsules complied with the quality control tests for freshly prepared capsules and after one month of storage at room temperature and at 40 °C and 75% relative humidity. The dissolution profile of these capsules indicates immediate and high release of ASA, which is essential to ensure the required absorption. This study is of great importance for patients who need to take this dose of ASA. Pharmacists can prepare good-quality capsules with the desired ASA content using a 100-mg ASA tablet as a source of the active ingredient.

Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

Background and Objectives. In case of absent liquid dosage form, crushing a tablet or dispersing a capsule would be the most convenient option for using these drugs in patients with dysphagia difficulties. The aims of the study were to prepare an extemporaneous suspension of amlodipine and valsartan from the available commercial tablets and to evaluate the stability and dissolution properties of the compounded suspension. Method. Amlodipine/valsartan extemporaneous suspension was prepared from available commercial tablets such as Valzadepine®. The dissolution profiles for the extemporaneous preparation and the commercial tablet were determined in different pH media. The physical, chemical, and microbial stability of the compounded formulation was evaluated over one-month period at room temperature. Moreover, in silico modeling using GastroPlus™ software was used to build absorption models for both drugs based on the in vitro dissolution data. The simulated plasma profiles for both active ingredients were compared with the in vivo plasma profiles to examine the similarity of the extemporaneous suspension and the commercial tablets. Results. The amlodipine/valsartan extemporaneous suspension was successfully prepared with acceptable organoleptic properties. The suspension was stable for four-week period preserving its physical and chemical features. The release profiles of valsartan and amlodipine from the suspension were similar to those from source tablet Valzadepine®. In silico modeling predicted the similarity of the extemporaneous suspension and the commercial tablets. Conclusion. Amlodipine/valsartan extemporaneous suspension could be prepared from available commercial tablets. Moreover, GastroPlus™ can be applied along with the in vitro dissolution in order to affirm similarity in extemporaneous compounding situations.

Assessing a Mass-Based Method for the Preparation of Low-Dosed Paediatric Capsules with Baclofen and Spironolactone

Despite the steadily improving medical care situation in pediatrics, some drugs are still not available in a suitable dose or dosage form and thus need to be prepared extemporaneously. Capsules can be easily compounded at the hospital and public pharmacies, offering an alternative to liquid formulations. This study aims at testing a mass-based approach for the extemporaneous preparation of low-dose pediatric capsules and investigating systematically the API loss during this procedure. A total of 54 capsule batches were prepared with baclofen and spironolactone as pediatric-relevant drugs. The hard capsules were prepared using three different bulking agents consisting of either mannitol, lactose-monohydrate and microcrystalline cellulose mixed with 0.5% colloidal silica. Capsules were tested according to Ph. Eur. method “2.9.40 Content Uniformity” as well as for occurring powder loss and mass uniformity. The results reveal that the mass-based approach, in general, allows the preparation of low-dose pediatric capsules of appropriate quality. However, absolute quality is highly dependent on the homogeneity of the powder mixture and the use of defined parameters for capsule preparation.

Stability of extemporaneous rifampicin prepared with X-temp® oral suspension system

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.

Trends of ex tempore drug preparation in Ukraine. Ways of their introduction into the practice

Background. Advantages of the ex tempore formulation include the ability to provide the drug in the form and dosage, not available on the pharmaceutical market, but necessary for a particular patient; the ability to include the required ingredient in any desired form; the option of combining drugs; the manufacture of drugs without flavorings, preservatives and stabilizers; the possibility of adjusting of the drug taste; the possibility of manufacturing drugs that are in short supply on the market; no possibility of counterfeiting; production of specific drugs. Objective. Assess the current situation and trends in the preparation of oncological drugs ex tempore. Materials and methods. Analysis of the literature on this topic. Results and discussion. In oncology the possibilities of ex tempore preparation include the manufacture of chemotherapeutic agents with individual dosage, of any adjuvant agents without excipients, of radiopharmaceuticals, combined and orphan drugs. In Ukraine, ex tempore formulation is not widespread: as of 2017, the percentage of drugs prepared in such way was 1.7 %, in 2018 – 1.43 %, in 2019 – 1.41 %. The situation is different in the European Union. For instance, in Poland the pharmacy receives a license only after creating the conditions for the manufacture of drugs, in Estonia any pharmacy must be able to produce non-sterile drugs, in Latvia 50 % of pharmacies have a license to manufacture drugs. The popularity of ex tempore preparation is also growing in the other countries (Australia, USA, Brazil, Jordan). The main areas of application of ex tempore drugs include hormone replacement therapy, analgesia, dermatology, chemotherapy, ophthalmology, treatment of orphan diseases, parenteral nutrition. Civilized countries often choose to develop the hospital pharmacy. However, there are a number of problems, including the lack of well-trained staff, the high cost of equipment and maintenance of sterile facilities, the constant changes in regulatory requirements and the need to gain the consumers’ respect. Conclusions. 1. Ex tempore drug preparation has a number of advantages, in particular, the ability to provide the drug in the individual form and dosage, the ability to combine drugs and the manufacture of specific drugs. 2. Extemporaneous preparation of drugs is especially important for oncology. 3. In contrast to European Union countries, ex tempore drug preparation is not widespread in Ukraine. 4. Problems of ex tempore drug preparation include lack of the staff, high equipment costs, and constant changes in regulatory requirements.

An Update on Extemporaneous Preparation of Radiopharmaceuticals Using Freeze-Dried Cold Kits

Abstract:: The field of nuclear medicine is rapidly evolving due to the high demand of radiopharmaceuticals for diagnostic and therapeutic applications. The availability of a vast array of radioisotopes, improvement in radiolabeling strategies, and advancements in detection systems have also contributed to the progress in this field. Radiopharmaceuticals are mainly classified based on their application as diagnostic or therapeutic radiopharmaceuticals. These are available either as ready to use preparations or prepared at hospital radiopharmacy either using automated synthesis modules or by using freeze-dried cold kit formulations. Availability of freeze-dried cold kits for preparation of varied radiopharmaceuticals for targeting various organs and tissues played an essential role in the extensive use of 99mTc radiopharmaceuticals for diagnostic imaging by single-photon emission computed tomography (SPECT) imaging. Cold kits are especially suitable for the preparation of radiopharmaceuticals labeled with isotopes like 177Lu with relatively long half-life or radionuclides produced by radioisotope generators. A simplified procedure for the preparation of positron emission tomography (PET) radiopharmaceuticals is also desired to achieve images with higher resolution and sensitivity offered by PET. Robust kit formulations will simplify the preparation of PET radiopharmaceuticals and will contribute to extensive applications of positron emitters such as 68Ga. Several therapeutic radiopharmaceuticals are also being made using cold kits of the ligands. This review provides an update on diagnostic and therapeutic radiopharmaceuticals prepared using cold kits.

Organization of chemotherapeutic preparations in advance: Do we save or waste money?

Objective The development of oncology day-hospital activities contributes to increase quality of life of patients and consequently have changed their perception about waiting. The extemporaneous preparation of antineoplastic has become difficult to achieve given the increasing activity, and hospital pharmacists have taken up the challenge by the implementation of the antineoplastic preparation in anticipation. Because anticipation can lead to an important number of preparations to be discarded, we also develop a recycled process for other patients to limit these waste extra costs. We aim to demonstrate the positive balance of anticipated preparation in this 4-year study report. Data sources: This prospective study was conducted in a major European oncology day-hospital from January, 2012 to December, 2015. The data were extracted from our software WinSimbad™ and updated as needed. The number and cost-associated of preparation ungiven chemotherapy doses (recycled or discarded) were compared to the global drug budget of our hospital in order to not exceed 2%. Data summary: 303,100 antineoplastic have been prepared. Approximately 35% of them were anticipated with an average of 5,431±984 that were finally ungiven. Two-third was recycled and the cost of the ungiven preparations finally discarded represents 1.7±0.15% of the global drug budget. Conclusions This study assesses the drug wastage and its associated cost of this concept through a prospective study and discusses the cost of ungiven antineoplastic preparations. With prior consideration of the need to define the acceptable rate of discarded ungiven preparation, the hospitals with an high oncology day-hospital activity should implement this approach.

A Drug Content, Stability Analysis, and Qualitative Assessment of Pharmacists’ Opinions of Two Exemplar Extemporaneous Formulations

Despite a decline in the number of active pharmaceutical ingredients prepared extemporaneously using proprietary products, there remains a need for such products in the community (for example, liquid medicines for paediatrics which may be otherwise commercially unavailable). A lack of experience and quality assurance systems may have diminished pharmacist’s confidence in the extemporaneous preparation process; therefore, pharmacists were asked to prepare two proprietary products, omeprazole and amlodipine. The resulting products were characterised in terms of variability in drug quantity, stability, particle size and antimicrobial properties. Furthermore, a self-administered questionnaire was used to assess 10 pharmacists’ opinions on the perceived complexity of the extemporaneous compounding process and their overall confidence in the final extemporaneously compounded products. Drug content studies revealed that 88.5% and 98.0% of the desired drug content was obtained for omeprazole and amlodipine, respectively. Antimicrobial properties were maintained for both drugs, however variability in particle size, particularly for amlodipine, was evident between formulations. While pharmacists who partook in the study had some or high confidence in the final products, they reported difficulty formulating the suspensions. Findings from this study provide insight into pharmacists’ views on two extemporaneously prepared products and highlight the variability obtained in preparations prepared by different pharmacists.