In direct compression of tablets, it is crucial to maintain content uniformity within acceptable margins, especially in formulations with low drug loading. To assure it, complex and multistep mixing processes are utilized in the industry. In this study, we suggest the use of a simple segregation test to evaluate mixing process performance and mixture segregation to produce tablets having satisfying content uniformity while keeping the process as simple and low cost as possible. Eventually, the formulation propensity to segregation can be evaluated using process analytical technology (PAT) to adjust the mixing process parameters to changing source drug properties. In this study, that approach was examined on a model drug with a broad batch-to-batch variability in particle size and shape. Excipients were chosen so that the resulting blend composition mimicked some marketed formulations. For each drug batch, two formulation blends were prepared through different preparation processes (one simple and one complex) and subsequently subjected to segregation tests. From those, segregation coefficients were obtained to compare segregation tendencies and homogeneity robustness between the drug batches and the blend preparation methods. The inter-particulate interactions were substantially influenced by the drug particle morphology and size and resulted in different segregation behavior. Based on these findings, a simple segregation test proved to be a useful tool for determining the suitability of different batches of the model drug to be used in a certain formulation. Moreover, for a particular batch A, the test revealed a potential for mixing process simplification and therefore process intensification and cost reduction.
PURPOSE: The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots. METHODS: An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables. RESULTS: Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates. CONCLUSIONS: PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.
- MeSH
- Cost-Benefit Analysis MeSH
- Analysis of Variance MeSH
- Antipsychotic Agents economics therapeutic use MeSH
- Benzodiazepines economics therapeutic use MeSH
- Chronic Disease MeSH
- Adult MeSH
- Economics, Pharmaceutical MeSH
- Isoxazoles economics therapeutic use MeSH
- Quality-Adjusted Life Years MeSH
- Delayed-Action Preparations economics therapeutic use MeSH
- Humans MeSH
- Decision Support Techniques MeSH
- Young Adult MeSH
- Multivariate Analysis MeSH
- Drug Costs * MeSH
- Olanzapine MeSH
- Paliperidone Palmitate MeSH
- Palmitates economics therapeutic use MeSH
- Risperidone economics therapeutic use MeSH
- Schizophrenia diagnosis drug therapy economics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
... -- 1.3.1 Causal Networks as Oracles for Interventions 22 -- 1.3.2 Causal Relationships and Their Stability ... ... Nontemporal Causation and Statistical Time 57 -- 2.9 Conclusions 59 -- 2.9.1 On Minimality, Markov, and Stability ... ... 171 -- 5.6.2 Identification in Linear Models 171 -- 5.6.3 Robustness of Causal Claims 172 -- 6 Simpson ... ... Definitions 184 -- 6.3 How the Associational Criterion Fails 185 -- 6.3.1 Failing Sufficiency via Marginality ...
1st ed. xii, 384 s.
- MeSH
- Causality MeSH
- Probability MeSH
- Conspectus
- Přírodní vědy. Matematické vědy
- NML Fields
- přírodní vědy
- statistika, zdravotnická statistika
