Development of an Optimised Application Protocol For Sonophoretic Transdermal Delivery of a Model Hydrophilic Drug

It has now been known for over a decade that low frequency ultrasound can be used to effectively enhance transdermal drug penetration - an approach termed sonophoresis. Mechanistically, acoustic cavitation results in the creation of defects in the stratum corneum that allow accelerated absorption of topically applied molecules. The aim of this study was to develop an optimised sonophoresis protocol for studying transdermal drug delivery in vitro. To this end, caffeine was selected as a model hydrophilic drug while porcine skin was used as a model barrier. Following acoustic validation, 20kHz ultrasound was applied for different durations (range: 5 s to 10 min) using three different modes (10%, 33% or 100% duty cycles) and two distinct sonication procedures (either before or concurrent with drug deposition). Each ultrasonic protocol was assessed in terms of its heating and caffeine flux-enhancing effects. It was found that the best regimen was a concurrent 5 min, pulsed (10% duty cycle) beam of SATA intensity 0.37 W/cm2. A key insight was that in the case of pulsed beams of 10% duty cycle, sonication concurrent with drug deposition was superior to sonication prior to drug deposition and potential mechanisms for this are discussed

Development of coated beads for oral controlled delivery of cefaclor: In vitro evaluation

The aim of the present study was to develop and characterize coated chitosan-alginate beads containing cefaclor as controlled release delivery system. Coated cefaclor beads were prepared by solvent evaporation techniques. Beads were found to be intact and spherical in shape. Their particle size range was 1.05 to 2.06. The loading efficiency showed maximum value when the concentration of cefaclor, chitosan and PEG 400 was 10 % (m/V), 0.5 % (m/V) and 2 % (V/V), respectively. Best retardation of cefaclor release from chitosan-alginate beads was achieved by coating with 15 % of shellac in formula F19. A significant antimicrobial activity (p < 0.05) against Staphylococcus aureus and Klebsiella pneumoniae was observed for formula F19 compared to the standard antibiotic disc. Furthermore, the simulated plasma profile showed the superiority of F19 in sustaining drug release for more than 12 h. Therefore, shellac coated chitosan-alginate beads could be considered as a successful controlled release oral cefaclor dosage form

Physical characterization and in vitro evaluation of some generic medications available in pharma market of United Arab Emirates (UAE)

This study is the first attempt in UAE to prove the trustworthiness of the in vitro evaluation to assess the reliability of the generic medications comparing to the brand name. Five generic medicines, two Local (codes: L1, L2), three Arabic (codes: A1, A2 and A3) and the International brand (code: I1) of diclofenac sodium (DS) sustained release tablets, as a model product, was collected randomly from the UAE pharma market. The products were characterized by physical parameters including weight variation, thickness, friability, hardness and moisture content. The in vitro release study was conducted in simulated gastric medium (0.1 N HCl, pH 1.2) for 2 h and simulated intestinal medium (phosphate buffer pH 6.8) for 9 h using type II (paddle type) USP reference dissolution apparatus. The drug was assayed by using UV spectrophotometry at 277 nm. Different kinetics models were applied to drug release data in order to evaluate mechanism of drug release. Physical properties of all products compiled with the acceptable limits. However moisture content was higher than the standard value in the generic products except the brand. All the products succeed to fulfill their official requirement of 80 % drug release within 8 h, in simulated intestinal medium except A3. Zero order release kinetics was predominant for al L2 and the International brand while more data fitting to Hixson- Crowell kinetics was obtained with the L1 and A1, A2 and A3. The results of our study question the suitability of the generic products as a replacement for the branded product. Therefore, we strongly suggest that evaluation on the marketed samples has to be made in order to establish bioequivalency between the branded and the generic products.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The Optimization of a Dimenhydrinate Transdermal Patch Formulation Based on the Quantitative Analysis of In Vitro Release Data by DDSolver through Skin Penetration Studies

Dimenhydrinate is an over-the-counter medication that is used to relieve nausea, vomiting, and vertigo caused by motion sickness. It has a short elimination half-life, possibly due to its first-pass metabolism. The current study aimed to prepare and evaluate new transdermal formulations of dimenhydrinate to prolong the drug’s release and improve its cutaneous permeation. First, the patches were fabricated and evaluated to determine their properties. The results were statistically investigated and considered significant at the p &lt; 0.05 level. Additionally, the quantitative analysis of the drug-release data and kinetic modeling was performed by using the DDSolver software to decide the candidate formula dependably. The effect of the penetration enhancers on the permeability of dimenhydrinate from the selected patch was then studied ex vivo compared to the control sample, and the patch’s safety was evaluated in rabbits, using the skin-irritation test

A Narrative Review of the Potential Roles of Lipid-Based Vesicles (Vesiculosomes) in Burn Management

Burn injuries can have a lasting effect on people&rsquo;s quality of life, as they negatively impact their physical and mental health. Then, they are likely to suffer psychological problems as a result. A serious problem is that deep burns are more challenging to treat due to their slow healing rate and susceptibility to microbial infection. Conventional topical medications used for burn treatment are sometimes ineffective because they cannot optimize their ability of transcutaneous absorption at the targeted site and accelerate healing. However, nanotechnology offers excellent prospects for developing current medical wound therapies and is capable of addressing issues such as low drug stability, water solubility, permeability, and bioavailability. The current review focuses on lipid-based vesicles (vesiculosomes) as an example of advanced delivery systems, showing their potential clinical applications in burn wound management. Vesiculosomes may help overcome impediments including the low bioavailability of active agents, offering the controlled release of drugs, increased drug stability, fewer side effects, and reduced dosing frequency, which will ultimately improve therapeutic efficacy and patient compliance. We discuss the application of various types of vesiculosomes such as liposomes, niosomes, ethosomes, cubosomes, transfersomes, and phytosomes in burn healing therapy, as these demonstrate superior skin penetration compared to conventional burn topical treatment. We also highlight their noteworthy uses in the formulation of natural products and discuss the current status as well as future perspectives of these carriers in burn management. Furthermore, the burn treatment options currently available in the market are also summarized

Formulation, Stability and Bioequivalency Study of Prepared Salbutamol Sulphate Nebules.

Salbutamol sulphate nebules is considered as the most rapid effective route of administration for treatment of acute attacks of asthma . This study was carried out to formulate a stable formula of salbutamol nebules containing 0.1% (2.5mg / 2.5ml) of the active ingredient in a buffered solution . Stability study in different buffers at pH 3 showed that the longest shelf life was equal to 3.5 years for formula F .In addition the bioequivalency of this formula incomparison to ventolin® nebules was measured and it was equal to (± 5.2) %. Also it was found that there was no significant difference between the formula and ventolin® nebules regarding their pharmacokinetic parameters which include elimination rate constant, elimination t 0.5 and amount of the unchanged drug excreted in urine, 30 min. after administration (p<0.05) . This study may suggest that the prepared formula could be used successfully in the preparation of salbutamol sulphate nebules

Employment of Alginate Floating In Situ Gel for Controlled Delivery of Celecoxib: Solubilization and Formulation Studies

Celecoxib (CXB) is a COX-2-selective nonsteroidal anti-inflammatory drug used to control pain and various inflammatory conditions. CXB has limited oral bioavailability and a slow dissociation rate due to its poor water solubility. In order to enhance the oral bioavailability of CXB and reduce the frequency of administration, the present study was aimed at enhancing the aqueous solubility of CXB by a cosolvency technique and then at formulating and evaluating a CXB in situ floating gelling system for sustained oral delivery. Three cosolvents, namely, PEG 600, propylene glycol, and glycerin, at different concentrations, were used to solubilize CXB. Particle size analysis was performed to confirm the solubility of CXB in the solutions. The floating in situ gel formulations were then prepared by the incorporation of the CXB solution into sodium alginate solutions (0.25, 0.5, and 1% w/v). Formulations, in sol form, were then in vitro characterized for their physical appearance, pH, and rheological behaviors, while formulations in gel form were evaluated for their floating behavior and in vitro drug release studies. FTIR spectroscopy was performed to examine drug-polymer interaction. The selected formula was evaluated biologically for its anti-inflammatory and analgesic activities. Results revealed that the less-polar solvent PEG 600 at 80% v/v had the highest solubilization potential, and it was used to optimize the in situ gel formulation. The candidate formula (F3) was found to have the highest sodium alginate concentration (1% w/v) and showed the optimum sustained release profile with the Higuchi model release kinetics. The results from the FTIR spectroscopy analysis showed noticeable drug-polymer molecular interaction. Moreover, F3 exhibited a significantly higher percentage of paw edema inhibition at 8 h compared with the reference drug (p<0.05). Also, it showed a sustained duration of analgesia that persisted for the entire experimental time

Professional practices and perception towards rational use of medicines according to WHO methodology in United Arab Emirates

Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. No study has been reported concerning rational drug use in United Arab Emirates, UAE, recently. Objectives: 1. assessing patterns of use and defining problems regarding the rational drug use. 2. Setting baseline situational analysis study for practices in the health care system relevant to drug use. Method: A descriptive pilot study, consisting of pharmacists, physicians and patients (100 of each of category) from four private hospitals, (12) medical clinics, (80) community pharmacies in addition to 150 prescriptions. A questionnaire of three sections was designed to include WHO indicators regarding patients, facility and prescribing patterns that are relevant to rational drug use was carried out in four emirates of the UAE in the period December 2008- Febreuary 2009. Results: Consultation and dispensing times were 10 (SD=2.75) min and 68 (SD=9.7) seconds, respectively. Average no. of drugs per prescription was (2.9 + 0.97), % of prescriptions using generic name (7.35%), % of antibiotic containing prescriptions (31.1%), % of injection containing prescriptions (2.9%), adherence to Standard Treatment Protocols (46%), adherence to the essential drug list (64%), patient´s knowledge of correct dosage (55%), adequately labeled drugs (45%), patient´s information (65%). Conclusions: Several areas of deficiency in rational drug use had been defined in the private sector through UAE that can be remedied through adopting several strategies such as adherence to national standard treatment guidelines and essential drug list based on treatments of choice, interaction between health care system and providing drugs information to consumers.La prescripción inapropiada reduce la calidad de la atención médica y lleva a un desperdicio de recursos. No se ha escrito ningún estudio sobre el uso racional de medicamentos en los Emiratos Árabes Unidos (EAU) recientemente. Objetivos: 1, evaluar los patrones de uso y definir problemas en el uso racional de medicamentos. 2, establecer la situación de base para el estudio de prácticas en el sistema sanitario relevantes al uso de medicamentos. Métodos: Estudio piloto descriptivo, incluyendo farmacéuticos, médicos y pacientes (100 de cada categoría) de 4 hospitales privados, (12) consultas médicas, (80) farmacias comunitarias además de 150 prescriptores. Se diseñó un cuestionario de tres secciones incluyendo los indicadores de la OMS relativos a pacientes, local y patrones de prescripción relevantes al uso racional de medicamentos para los cuatro emiratos de EAU en el periodo de diciembre 2008 a febrero 2009. Resultados: los tiempos de consulta y dispensación fueron e 10 (SD=2,75) minutos y 68 (SD=9,7) segundos respectivamente. La media de medicamentos por receta fue de 2,9 (SD=0,97), el 7,35% de las recetas usaban nombres genéricos, el 31,1% contenía antibióticos, el 2,9% contenía inyectables, el 46% cumplía los protocolos estándar de tratamiento, el 64% contenía medicamentos de la lista de medicamentos esenciales, en el 55% había conocimiento de los pacientes de la dosis correcta, en el 45 hubo etiquetado adecuado de los medicamentos, y en el 65% hubo información a los pacientes. Conclusiones: Se identificaron varias deficiencias en cuento al uso racional de medicamentos en el sector privado en los EAU que pueden remediarse adoptando algunas estrategias como el cumplimiento de las guías de estándares nacionales tratamientos y la lista de medicamentos esenciales para la elección de tratamientos, la interacción entre el sistema sanitario y los proveedores de información sobre de medicamentos a los consumidores

Pomegranate extract-loaded sphingosomes for the treatment of cancer: Phytochemical investigations, formulation, and antitumor activity evaluation.

AimFormulation of Pomegranate Extracts (PE)-loaded sphingosomes as an antitumor therapy for the intravenous and passive targeted delivery to various tumor types, especially that of the breast, colon, and uterus; to increase the therapeutic activity and decrease the adverse effects profile.MethodsThe pericarp and seeds' juice of Punica granatum were each extracted using D.W. and ethanol. Phytochemical investigation of all extracts was carried out including total phenolics, flavonoids, and anthocyanins contents, the antioxidant activity, as well as HPLC analysis of phenolics and flavonoids. The antitumor potential of all extracts was also tested utilizing three cell lines: MCF-7, HeLa, and HCT116. The candidate extract was chosen for the formulation phase and was entrapped into the sphingosomes using the thin-film hydration method and employing three different PE: lipids weight ratios. The synthesized formulations were characterized for their size, morphological features, zeta potential, entrapment efficiency, and in vitro drug release and kinetics modeling studies. The optimized formula was further analyzed by FTIR spectroscopy and electron microscopy. The antitumor activity of F2 was also investigated using the same cancer cell lines compared to the plant extract.ResultsThe highest phenolics, flavonoids, and anthocyanins contents were observed in the ethanolic pericarps extract (EPE), followed by the ethanolic seeds extract (ESE). Consequently, EPE showed a higher antitumor activity hence it was selected for the formulation phase. PE-loaded sphingosomes formula (F2) was selected for having the highest EE% (71.64%), and a sustained release profile with the highest in vitro release (42.5±9.44%). By employing the DDSolver, the Weibull model was found the most suitable to describe the PE release kinetics compared to other models. The release mechanism was found to follow Fickian diffusion. Simulated pharmacokinetic parameters have portrayed F2 as the candidate formula, with the highest AUC (536.095) and slowest MDT (0.642 h). In addition, F2 exhibited a significant (p>0.05) stronger and prolonged anticancer effect against MCF-7, HeLa, and HCT116 cell lines at all concentrations tested compared to the free extract.ConclusionThe results proved that sphingosomes are an effective delivery system, improving pharmacological efficacy and reducing serious side effects of anticancer medications and natural products