Measure, caracterisation and prediction of drugs stability

The development of a hospital pharmaceutic formulation implies an a priori analysis of feasibility and risk. During this analysis, the pharmacist responsible of the formulation development must take a decision about the theoretical risk of instability of the formulation. Then, a prospective analysis of the formulation stability is done. This evaluation is inevitable. It is time consuming, costly, requires equipment and has a risk of failure. This work presents a scientific introduction about kinetic modelling applied to stability studies. During this literature review, the chemical and physical reaction pathways and the impact of temperature and humidity are depicted in mathematical models. Then, two approaches are introduced. The first one proposes a total prediction of the degradation kinetic of an active pharmaceutical ingredient in its formulation. This method is presented and applied to the pharmaceutical development of a formulation. Due to its huge need of computer resources, its applicability will be limited. The second approach is a semi predictive stability assessment. During this method, a few sets of experimental data is compared to a set of kinetic models. The best fitted model is chosen and then extrapolated to predict the stability of a formulation. This method is presented in chapter III and successfully applied to the prediction of the stability of two drugs. Finally, stability data are compared to molecular descriptors and physicochemical property of the studied active pharmaceutical ingredients to understand their impact.The development of a hospital pharmaceutic formulation implies an a priori analysis of feasibility and risk. During this analysis, the pharmacist responsible of the formulation development must take a decision about the theoretical risk of instability of the formulation. Then, a prospective analysis of the formulation stability is done. This evaluation is inevitable. It is time consuming, costly, requires equipment and has a risk of failure. This work presents a scientific introduction about kinetic modelling applied to stability studies. During this literature review, the chemical and physical reaction pathways and the impact of temperature and humidity are depicted in mathematical models. Then, two approaches are introduced. The first one proposes a total prediction of the degradation kinetic of an active pharmaceutical ingredient in its formulation. This method is presented and applied to the pharmaceutical development of a formulation. Due to its huge need of computer resources, its applicability will be limited. The second approach is a semi predictive stability assessment. During this method, a few sets of experimental data is compared to a set of kinetic models. The best fitted model is chosen and then extrapolated to predict the stability of a formulation. This method is presented in chapter III and successfully applied to the prediction of the stability of two drugs. Finally, stability data are compared to molecular descriptors and physicochemical property of the studied active pharmaceutical ingredients to understand their impact

Mesure, caractérisation et prédiction de la stabilité des médicaments

The development of a hospital pharmaceutic formulation implies an a priori analysis of feasibility and risk. During this analysis, the pharmacist responsible of the formulation development must take a decision about the theoretical risk of instability of the formulation. Then, a prospective analysis of the formulation stability is done. This evaluation is inevitable. It is time consuming, costly, requires equipment and has a risk of failure. This work presents a scientific introduction about kinetic modelling applied to stability studies. During this literature review, the chemical and physical reaction pathways and the impact of temperature and humidity are depicted in mathematical models. Then, two approaches are introduced. The first one proposes a total prediction of the degradation kinetic of an active pharmaceutical ingredient in its formulation. This method is presented and applied to the pharmaceutical development of a formulation. Due to its huge need of computer resources, its applicability will be limited. The second approach is a semi predictive stability assessment. During this method, a few sets of experimental data is compared to a set of kinetic models. The best fitted model is chosen and then extrapolated to predict the stability of a formulation. This method is presented in chapter III and successfully applied to the prediction of the stability of two drugs. Finally, stability data are compared to molecular descriptors and physicochemical property of the studied active pharmaceutical ingredients to understand their impact.The development of a hospital pharmaceutic formulation implies an a priori analysis of feasibility and risk. During this analysis, the pharmacist responsible of the formulation development must take a decision about the theoretical risk of instability of the formulation. Then, a prospective analysis of the formulation stability is done. This evaluation is inevitable. It is time consuming, costly, requires equipment and has a risk of failure. This work presents a scientific introduction about kinetic modelling applied to stability studies. During this literature review, the chemical and physical reaction pathways and the impact of temperature and humidity are depicted in mathematical models. Then, two approaches are introduced. The first one proposes a total prediction of the degradation kinetic of an active pharmaceutical ingredient in its formulation. This method is presented and applied to the pharmaceutical development of a formulation. Due to its huge need of computer resources, its applicability will be limited. The second approach is a semi predictive stability assessment. During this method, a few sets of experimental data is compared to a set of kinetic models. The best fitted model is chosen and then extrapolated to predict the stability of a formulation. This method is presented in chapter III and successfully applied to the prediction of the stability of two drugs. Finally, stability data are compared to molecular descriptors and physicochemical property of the studied active pharmaceutical ingredients to understand their impact

Measurement, analysis and prediction of amoxicillin oral dose stability from integrated molecular description approach and accelerated predictive stability (APS)

Stability of low amoxicillin oral dosage form (5 mg) used in reintroduction drug test was not fully documented. Furthermore, the impact of (1) salt moiety of amoxicillin and (2) amoxicillin – excipient interactions upon the antibiotic formulation stability during the storage was not characterized so that the estimation of the pharmaceutical expiration date from shelf-life was uncertain. Thus, the main goal of this study was to estimate the shelf-life of two formulations of amoxicillin, using a semi-predictive methodology

J Pharm Biomed Anal

Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0.1-200ng/ml, 1-200ng/ml, 4-800ng/ml and 25-5000ng/ml. Solid phase extraction was used and separation was performed with HPLC using a gradient system on a solid core particle C18 column (5x2.1mm, 1.6mum). Ions were detected with a triple quadrupole mass spectrometry system. This assay allows rapid determination of 19 TKI in less than 5min per run. This high throughput routine method will be useful to adjust doses of oral anticancer drugs in order to improve treatments efficacy

Recommendations on training objectives and staff qualification for the manual preparation of capsules in pharmacy

International audienceTraining and certification of personnel in capsule preparation are essential procedures, overseen by the pharmacist who delegates these tasks. These procedures aim not only to ensure the efficacy and safety of operations but also to establish a clear chain of responsibility. They align with established best practices. Certification grants formal authorization to qualified individuals to perform specific tasks. For new hires, a comprehensive training program is designed to facilitate their integration and empower them from the onset. We propose training objectives structured around a competency-based approach, highlighting objective evaluation criteria applicable in real-world practical settings. These training objectives address critical aspects such as the handling of hazardous substances, weighing and mixing of powders, and capsule filling. They also emphasize the importance of documentation and traceability. Specialized preparations and tools are offered to facilitate the assessment of learning outcomes