3D Printed Buccal Films for Prolonged-Release of Propranolol Hydrochloride: Development, Characterization and Bioavailability Prediction

Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties and drug release profiles of gelatin-based films. The Fourier-transform infrared spectroscopy showed that hydrogen bonding between gelatin and PVP formed during printing. In the other blend, neither the esterification of PVA nor gelatin occurred. Differential scanning calorimetry revealed the presence of partial helical structures. In line with these results, the mechanical properties and drug release profiles were different for each blend. Formulation with gelatin-PVP and PRH showed higher tensile strength, hardness, and adhesive strength but slower drug release than formulation with gelatin-PVA and PRH. The in silico population simulations indicated increased drug bioavailability and decreased inter-individual variations in the resulting pharmacokinetic profiles compared to immediate-release tablets. Moreover, the simulation results suggested that reduced PRH daily dosing can be achieved with prolonged-release buccal films, which improves patient compliance.

Method Development and Validation for the Estimation of Etizolam and Propranolol Hydrochloride in bulk and Combined Dosage Forms by Simultaneous and Derivative Spectroscopic Methods

Accurate, simple, sensitive and rapid economic UV spectroscopic methods were developed for the estimation of Etizolam and Propranolol Hydrochloride in bulk and combined dosage form. The present study deals with the UV spectroscopic method development and validation for the Simultaneous Equation method and First Derivative method of Etizolam and Propranolol Hydrochloride in bulk and combined dosage form at determined wavelength of Etizolam and Propranolol Hydrochloride at 244nm and 288nm for Simultaneous Equation method and 234nm and 289nm for First Derivative Method. The linearity range for Etizolam and Propranolol Hydrochloride was 1-5µg/ml and 10-50µg/ml, and exhibit good correlation coefficient of Etizolam and Propranolol Hydrochloride was 0.9877 and 0.9977 for Simultaneous Equation method and 0.9872 and 0.9977 for First Derivative method, respectively and excellent mean recovery (98-102%). The precision was found to be within limit (%RSD <2). Comparatively First Derivative method is more sensitive than Simultaneous Equation method. The methods were validated statistically and parameters like linearity, precision, accuracy, specificity and assay was studied according to ICH guidelines and can be applicable in determination of both drugs in routine quality control analysis of drugs in bulk and combined dosage form.

PSIX-17 Cytokine profile of cow blood in the treatment of acute postpartum endometritis with recombinant α -, γ-interferons

The aim of the study was to research the cytokine profile of cow blood in the treatment of acute postpartum endometritis with the use of recombinant α-, γ-interferons. Animals of the first group (n = 9) with a diagnosis of acute postpartum endometritis were intramuscularly injected with propranolol hydrochloride, denatured emulsified placenta, and nioxityl. Propranolol hydrochloride was administered for 4 days at a dose of 10 ml/animal at 24-hour intervals. The denatured emulsified placenta was injected subcutaneously on days 1-5-9 at a dose of 25 ml /animal. Nioxityl was injected intrauterine at a dose of 150 ml three times with a 48-hour interval. Cows of the second group (n = 11) with the same diagnosis were additionally injected intramuscularly with bovine recombinant α-, γ-interferons three times in 1–3 days at a dose of 5 ml/animal, 1 cm3 of which contains at least 1x104 IU/cm3 of the total antiviral activity of bovine recombinant α-, γ-interferons. Blood samples are taken from all groups before and at the end of the experiment. Blood samples are examined for the content of interleukin-2 (IL-2), interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10) using Bovine Elisa Kit Clood-Clone Corp (USA). The therapeutic effectiveness in the first group was 77.8%, in the second - 90.9%, which is 13.1% more. At the end of the course, the level of IL-2 decreased by 42.5% (43.5±4.2 pg/ml, P &lt; 0.01), TNF-Α by 9.1% (457.9±34.6 pg/ml), the level of IL-4 increased by 14.8% (44.2±3.5 pg/ml, P &lt; 0.05), IL-10 by 56.6% (35.7±2.8 pg/ml, P &lt; 0.01). In the second group, the level of anti-inflammatory cytokines decreased: IL–2 by 48.7% (38.8±1.6 pg/ml, P &lt; 0.01), TNFα by 26% (372.5±17.6 pg/ml, P &lt; 0.05) and increased anti–inflammatory cytokines: IL-4 by 46.2% (56.3±4.1 pg/ml, P &lt; 0.001) and IL-10 by 80.3% (41.1±3.5 pg/ml, P &lt; 0.001), which indicates a decrease in the inflammatory response.

The Association of Propranolol with 2DG Reduces the Metabolism and the Proliferation of Cutaneous Squamous Cell Carcinoma A431 Cell Line

The non-selective β-blocking (±)-Propranolol Hydrochloride was demonstrated to improve the progression-free survival of patients and to reduce the incidence of different cancer types. Since the expression of β-adrenoceptors (β-AR) in the A431 squamous cell carcinoma (cSCC) human cells was described, we had suggested that cSCC proliferation may be controlled by using β-AR-blockers. Thus, we hypothesized that the topical application of a β-AR-blocker over the tumor lesion may decrease/restrain its extension before the surgical excision becoming an adjuvant\therapy against cSCC. However, it is known that β-AR-blocker anti-cancer activity as a single agent is limited. Hence, we suggested that the combination of Propranolol with the glucose analog 2-Deoxy-D-glucose (2-DG) could improve its antiproliferative effect through the induction of metabolic stress. Our results have demonstrated that the addition of 2DG to (±)-Propranolol Hydrochloride therapy can improve its effect on A431 cells metabolism and proliferation, suggesting that the combination of (±)-Propranolol Hydrochloride with low dose of 2DG could be a promising treatment to be topically applied as an adjuvant pre-surgical therapy against cSCC, aiming to decrease the size of the injury before the surgical procedure, avoiding systemic adverse effects to the patient.