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Abstract: Background: The photodegradation of drugs obeying unimolecular mechanisms such as that of nifedipine (NIF) were usually characterised in the literature by zero-, first- and second-order kinetics. This approach has been met with varying success. This paper addresses this issue and proposes a novel approach for unimolecular photodegradation kinetics. The photodegradation of the cardiovascular drug nifedipine is investigated within this framework. Methods: Experimental kinetic data of nifedipine photodegradation were obtained by continuous monochromatic irradiation and DAD analysis. Fourth-order Runge–Kutta calculated kinetic data served for the validation of the new semi-empirical integrated rate-law model proposed in this study. Results: A new model equation has been developed and proposed which faithfully describes the kinetic behaviour of NIF in solution for non-isosbestic irradiations at wavelengths where both NIF and its photoproduct absorb. NIF absolute quantum yield values were determined and found to increase with irradiation wavelength according to a defined sigmoid relationship. The effects of increasing NIF or excipients’ concentrations on NIF kinetics were successfully modelled and found to improve NIF photostability. The potential of NIF for actinometry has been explored and evaluated. A new reaction order (the so-called Φ-order) has been identified and specifically proposed for unimolecular photodegradation reactions. Conclusion: The semi-empirical and integrated rate-law models facilitated reliable kinetic studies of NIF photodegradation as an example of AB(1Φ) unimolecular reactions. It allowed filling a gap in kinetic studies of drugs since, thus far, thermal first-order or a combination of first- and zero- order kinetic equations were generally applied for drug photoreactions in the literature. Also, a new reaction order, the “Φ-order”, has been evidenced and proposed as a specific alternative for photodegradation kinetics. [Copyright &y& Elsevier]

Abstract: Pharmaceutical regulatory bodies require minimal presence of solvent in an active pharmaceutical ingredient (API) after crystallization. From a processing point of view bigger crystals with minimal agglomeration and uniform size distribution are preferred to avoid solvent inclusion and for improved downstream processing. The current work addresses these issues encountered during the production of the potential anti-arrhythmic cardiovascular drug, AZD7009. This paper demonstrates that by applying the automated direct nucleation control (ADNC) approach problems with agglomeration and solvent inclusion were resolved. This model free approach automatically induces temperature cycles in the system, with the number of cycles, temperature range and adaptive heating and cooling rates determined to maintain the number of particles in the system, as measured by a focused beam reflectance measurement (FBRM) probe, within a constant range during the crystallization. The ADNC approach was able to produce larger and more uniform crystals and also removed the residual solvent trapped between the crystals compared to the typical crystallization operation using linear cooling profile. The results illustrate the application of process analytical technologies, such as FBRM and ATR-UV–vis spectroscopy, for the design of optimal crystallization operating conditions for the production of pharmaceuticals, and demonstrate that the ADNC approach can be used for rapid crystallization development for APIs exhibiting problems with agglomeration and solvent inclusion. [Copyright &y& Elsevier]

This paper explores the influence of initial molecular weight and porosity on the release of the drug, theophylline, from polyglycolide (PGA). PGA was made by a variety of processes to vary the molecular weight and was blended with NaCl with different crystal sizes and in different proportions to vary the pore size and volume. Overall, results showed that decreasing the molecular weight and increasing the pore size and volume increased the rate of drug release. The exact variation of these trends agreed well with the previously established four-stage degradation mechanism for PGA, but was more complex than a simple linear behaviour. Because both the molecular weight and the porosity of PGA have a substantial influence on the polymer degradation, and can be varied in a controlled manner, these parameters can play an important role in developing PGA as a controlled drug delivery material with tailored drug release. [Copyright &y& Elsevier]

Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared. [ABSTRACT FROM AUTHOR]