Search

[Display omitted] With the growing interest in environmentally friendly and personalized medicines, new concept for combining three-dimensional printing (3DP) with natural-based biomaterials derived from agro-food wastes has emerged. This approach provides sustainable solutions for agricultural waste management and potential for developing of novel pharmaceutical products with tunable characteristics. This work demonstrated the feasibility of fabricating personalized theophylline films with four different structures (Full, Grid, Star, and Hilbert) using syringe extrusion 3DP and carboxymethyl cellulose (CMC) derived from durian rind wastes. Our findings suggested that all the CMC-based inks with shear thinning properties capable of being extruded smoothly through a small nozzle could potentially be used to fabricate the films with various complex printing patterns and high structural fidelity. The results also demonstrated that the film characteristics and release profiles could be easily modified by simply changing the slicing parameters (e.g., infill density and printing pattern). Amongst all formulations, Grid film, which was 3D-printed with 40 % infill and a grid pattern, demonstrated a highly porous structure with high total pore volume. The voids between printing layers in Grid film increased theophylline release (up to 90 % in 45 min) through improved wetting and water penetration. All findings in this study provide significant insight into how to modify film characteristics simply by digitally changing the printing pattern in slicer software without creating a new CAD model. This approach could help to simplify the 3DP process so that non-specialist users can easily implement it in community pharmacies or hospital on demand. [ABSTRACT FROM AUTHOR]

Abstract: Generics are usually considered to exhibit comparable in vivo properties in terms of efficacy and safety and for this reason are intended to be interchangeable with the reference product. The aim of this study is to provide a quantitative picture of the switchability problem between two generics and to introduce the concept of conditional probability of bioequivalence (BE) acceptance. Monte Carlo simulations were performed to examine all possible relationships between the tested products. Four types of percent BE acceptances are defined and evaluated: (a) %BA1, when generic T1 is compared to the R product, (b) %BA2, in cases of comparison of generic T2 with the R product, (c) %BA21, when generic T2 is compared to another generic T1, and finally (d) %BA21C which is the conditional probability of percent bioequivalence acceptance of generic T2 versus another generic T1 given that both T1 and T2 are declared bioequivalent to the same R formulation. The simulations were expanded to study concomitantly the performance of T1 and T2 when compared to the same R formulation. In each case, the 2×2 cross-over design was used and evaluation of BE was based on the classic BE limits (0.80–1.25) and the stricter BE limits (0.90–1.11) for narrow therapeutic index (NTI) drugs. A number of 24 and 48 subjects were assumed to participate in the simulated trials, while the coefficient of variation for the within-subject variability (CVw) was 20% and 40%. A number 40,000 BE trials were simulated under each condition. The T1/R and T2/R ratios ranged from 0.80 to 1.25 using a step of 0.05. Even though two generics (T1 and T2) can be declared bioequivalent to the same R product, this does not ensure that they are always mutually bioequivalent. On the contrary, two generic products which differ substantially from the R product can still have a high probability to be truly interchangeable. The two generics (T1 and T2) can be switched from one to another when the T1/R and T2/R ratios are close to the same value, the CVw of the drug is low, and each BE study of T1–R and T2–R was conducted using a relatively large number of subjects. In the same context, two generic NTI drugs which differ more than 10% from the R product can still be declared bioequivalent to one another depending on the relative T1/R and T2/R ratios. Switchability between generics assessed at the 0.90–1.11 interval is safer, but not always ensured. [Copyright &y& Elsevier]

Objective: To generate patient-centered, evidence-based decision support tools and compile resources that will assist pharmacists in prescription drug product substitution activities and related communication, and to present the resulting tools and resources. Data Sources: Food and Drug Administration (FDA) publications, data, and communication; peer-reviewed literature; interviews with pharmacists; structured discussions with members of the project Advisory Board; and author's own knowledge and records of events. Summary: A decision whether to substitute an alternative product for a prescribed medication is a clinically based process that must be grounded in appropriate medical evidence, therapeutic equivalence information, financial factors, and consideration of how the substitution will impact the patient. Product substitution decisions are influenced by therapeutic issues, legal matters, patient-centered concerns, and pharmacy practice factors, including work flow, supply issues, access to current resources, and misperceptions about database information. While generic substitution is clearly defined in many cases, some medication categories require special consideration, i.e., critical dose and narrow therapeutic index drugs, products with special release mechanisms, bioengineered protein products, many hormonal products, older drugs marketed before 1938 that were not subject to FDA approval, and others with limited bioequivalence data. In response to reports of the challenges pharmacists face when determining the appropriateness of product substitution and in support of their interdisciplinary efforts to improve medication use, the American Pharmacists Association (APhA) convened an advisory board to create the decision support tool featured in this article. Conclusion: The U.S. health care system and patients rely on pharmacists as medication use experts to ensure that prescription drug product substitutions are appropriate. Pharmacists must be able to efficiently determine therapeutic equivalence, identify situations where further research is required, have access to timely resources for gathering information, and effectively communicate with patients and physicians about substitution issues. The prescription drug product substitution tool and related resources presented are intended to assist pharmacists in making and communicating clinically sound product substitution decisions that are patient centered, evidence based, consistent with state and federal laws and regulations, and reflective of the realities of health care today. [ABSTRACT FROM AUTHOR]