Design of a pilot plant-type pharmaceutical reactor to address the problem of interchangeability of generic semisolid formulations.

OBJECTIVE AND SIGNIFICANCE: This research aims to design and develop a pilot plant-type pharmaceutical reactor with a strong focus on its volumetric capacity and heat transfer capabilities. The primary goal is to replicate design and control strategies at the laboratory or pilot scale to analyze and produce generic semisolid formulations. METHODS: Computational fluid dynamics and heat transfer modeling, utilizing the finite volume method, were employed to determine the reactor's performance and particle trajectory during the mixing and stirring. This allowed for the establishment of optimal operational parameters and variables. Furthermore, prototypes were constructed at 1:2.5 and 1:15 scales to examine the reactor's morphology, ensure volumetric versatility, and conduct mixing, homogenization, and coloration tests using varying volumes. RESULTS AND CONCLUSIONS: The outcomes of this study yielded a versatile reactor suitable for processing pharmaceutical semisolids at both laboratory and pilot-scale volumes. Notably, the reactor demonstrated exceptional volumetric capacity within a single vessel while effectively facilitating heat transfer to its interior.

Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride.

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Rate of vision loss in neovascular age-related macular degeneration explored.

PURPOSE: To explore decline in visual acuity in patients with neovascular age-related macular degeneration (n-AMD) awaiting intravitreal bevacizumab or ranibizumab treatment following initial diagnosis and after disease reactivation. METHODS: Retrospective analysis of 74 treatment-naïve patients (84 eyes) in two centers in Córdoba, Argentina. The time between treatment indication and intravitreal injection, and the changes in BCVA produced during this delay were studied in both periods. A linear regression model to search the impact of time on progression visual impairment was conducted. RESULTS: In both periods, a significant reduction in vision occurred awaiting intravitreal injection. The longer the delay, the greater the vision loss (R2 = 0.55 p < 0.01) and the less improvement following treatment (Pearson coefficient -0.26). The result of the model shows that the change in vision as a function of initial delay were best described by a polynomic model with a mean loss of 5 letters in the first 3 weeks, a slowdown in the rate of change of VA, and a dependence of visual acuity at the moment of diagnosis . The loss of visual acuity after reactivation shows the same behavior as at the onset of the disease but independent of visual acuity prior to reactivation. CONCLUSION: Visual loss awaiting injection intravitreal anti-VEGF is clinically significant and with an asymptotic pattern, with early rapid loss of vision in both the onset of the disease and the reactivation. Initiation of anti-VEGF treatment must be undertaken urgently, as should retreatment of disease activation to reduce visual loss.

Accessibility as a conditioning factor in treatment for exudative age-related macular degeneration.

PURPOSE: Ranibizumab and bevacizumab coexist as the main therapeutic strategies for the treatment of neovascular age-related macular degeneration (NV-AMD). In Argentina, the access pathways to the drugs are different. Patients with different pathways and gatekeepers to access may experience different outcomes. The purpose of this work was to estimate the impact on therapeutic effects and visual outcome of the different accessibilities to NV-AMD treatment. 
 METHODS: A retrospective analysis of the charts of 78 patients with previously untreated exudative AMD, who were treated with ranibizumab or bevacizumab between January 2009 and December 2011, was conducted. The main outcomes measured included time delay and change in mean best-corrected visual acuity (BCVA) between diagnosis and treatment and mean BCVA change at 1-year follow-ups.
 RESULTS: The delay between diagnosis and treatment and decrease in visual acuity over this time was significantly higher for patients treated with ranibizumab. At 1 year after the initiation of treatment, BCVA had a mean increase from baseline of 0.11 letters in the bevacizumab group with a mean of 4.71 injections, compared with a decrease of 8.87 letters with a mean of 2.98 injections in the ranibizumab group.
 CONCLUSIONS: Access to treatment can be a key factor for success of therapy. Waiting times and availability of doses are crucial in the treatment of NV-AMD. Solving the problems related to delayed initiation of therapy and the difficulties in the maintenance phase are more important than define whether bevacizumab or ranibizumab is used.