Mechanical, optical, and physicochemical properties of HPMC-based doxazosin mesylate orodispersible films

Abstract In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product

Evaluation of Short Term Clinical Effects and Presumptive Mechanism of Botulinum Toxin Type A as a Treatment Modality of Benign Prostatic Hyperplasia

The purpose of this study was to evaluate the effect and investigate the putative mechanism of botulinum toxin type A (BTA) applied to the treatment of benign prostatic hyperplasia (BPH). A total of 52 patients with symptomatic BPH were evaluated. Transperineal intraprostatic injection under transrectal ultrasonography was carried out. BTA dissolved in 4 to 9 mL of saline was used from 100 U to 300 U, according to prostate volume. Twenty-six patients received only BTA (BT group), and 26 received both BTA and one month of an alpha-adrenergic antagonist (BTalpha group). The therapeutic outcomes were evaluated by comparing parameters such as international prostate symptom score (IPSS), quality of life, prostate specific antigen, prostate volume, post-void residual urine, and peak urinary flow rate. At the one month follow- up, 18 patients in the BT group and 21 in the BTalpha group had subjective symptomatic relief (p = 0.337). Only IPSS5 (weak stream) was significantly different between the BT group and BTalpha groups (p = 0.034). At the three month follow-up, 39 patients had subjective symptomatic relief. The storage symptoms were improved more than the voiding symptoms. Additionally, about 50 percent of the patients whose voiding symptom improved expressed improved erectile function. BTA injection seems to be an alternative treatment for BPH. The differences after the one month evaluation between the BT and the BTalpha groups might suggest that the adrenergic influence could be relatively reinforced by the anticholinergic effect of BTA. Nitric oxide would thus be involved in a BTA action mechanism in BPH.

Uso de doxazosin en la hiperplasia prostática benigna obstructiva: experiencia clínica / Use of doxazosin in the obstructive benign prostate hyperplasia: clinical experience

Mucho se ha publicado sobre farmacoterapia para el manejo de la hiperplasia prostática benigna, pero no está bien definido la existencia de influencia ambientales, genéticas o alimenticias sobre su desarrollo y la respuesta a los distintos medicamentos comercialmente disponibles. Un total de 24 pacientes son evaluados con un parámetro urodinámico (uroflujometría) a la administración de dosis creciente de doxazosin y se confirma su beneficio en mejoría de flujo, buena tolerancia y efectos positivos en bajas dosis, con efecto residual prolongada