EVALUATION OF INNOVATIVE CO-PROCESSED ADDITIVE FOR DIRECT COMPRESSION TABLETS USING ATORVASTATIN AND DIAZEPAM AS MODEL DRUGS

Objective: The aim of the present study is to prepare and evaluate a co-processed excipient from commercially available Avecil PH102 and silicon dioxide colloidal (SDC) using direct compression technique for preparation of tablets.Methods: The effect of the ratio of the two components on the properties of the prepared co-processed excipient has been investigated. In addition, it was evaluated for flowability, compressibility, and compatibility utilizing Fourier transforms Infrared (FTIR) and Differential scanning calorimetry (DSC) analysis. Tablets were produced by direct compression utilizing the co-processed additive with diazepam or atorvastatin calcium as model drugs in addition to magnesium stearate and talc as a lubricant. The addition of super disintegrant croscarmellose sodium or tablets preparation by wet granulation was utilized for comparison regarding the properties of prepared tablets. The prepared tablets were characterized for the drug content, hardness, friability, disintegration, dissolution, and stability.Results: Optimal physicochemical properties of the excipient from a manufacturing perspective were obtained using a co-processed Avecil PH102-with SDC (2% w/w) to get a mixture. The FTIR and DSC analysis showed no chemical interaction. The properties of tablets made using co-processed excipient showed good hardness, friability, acceptable tablet disintegration time, dissolution rate, and stability comparable to that obtained by the multistep method of wet granulation. Although the addition of super disintegrant more shorten the disintegration time but the obtained value without croscarmellose sodium is still satisfied the requirement.Conclusion: The Avecil PH102-SDC co-processed excipient produced was found to be promising as a valuable industrial, pharmaceutical excipient for the production of compressed tablets with good physical properties and fast dissolution.Â

STUDYING THE EFFECT OF DIFFERENT GELLING AGENT ON THE PREPARATION AND CHARACTERIZATION OF METRONIDAZOLE AS TOPICAL EMULGEL

Objective: Emulgels as topical dosage form recently gains an interest represent a combination of gels and emulsions in united form. Metronidazole is an antimicrobial and anti-inflammatory drug, as the first topical therapy approved for rosacea; metronidazole has remained a cornerstone of rosacea management. Methods: Emulgel formulations of metronidazole benzoate were prepared using two types of gelling agents, Carbopol 940 and hydroxypropyl methylcellulose, the influence of type and concentration of them on the release of metronidazole benzoate was investigated. The prepared formulations were evaluated on the basis of pH, spreadability, viscosity, drug content, in vitro release, and compatibility studies. Results: All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. Conclusion: The best formulation (F4) prepared using Carbopol 940 as gelling agent showed the highest drug release through 5 h

Food dyes as an alternative tracking dye for DNA gel electrophoresis

The chemical, physical and toxicological effects on health of synthetic dyes that used as tracking dye in the electrophoresis requires seriously search about alternative tracking dye. The present study is aimed to find an alternative dye from safe food dyes which commonly used in food coloring. Five dyes were selected depending on their chemical properties and the availability in local market: Brilliant Blue FCF, Tartrazine, Sunset Yellow FCF, Carmoisine, and green traditional, three dyes were chosen to be mixed as loading buffer: Brilliant Blue FCF, Sunset Yellow FCF as a basic because it give the whole range size of most traditional loading buffers that available in market, and adding the Carmoisine as a new indicator for the bands less than 50bp, then mixed with DNA ladder in same percentage used with traditional loading buffers to clarify the effects of dyes on DNA, migrated on 1% agarose with loading buffer promega, results showed more clarity and highly readable separation of dyes and give wide range of size in the food loading mix than promega loading dye, by viewing the gel on UV light the DNA ladder were moved smoothly, bands separated effeminately on gel and in same rate of the DNA ladder that load with promega loading buffer which indicate no interaction between the food dyes and the DNA.Our studies show that the food dye can be used as a tracking dye in place of used synthetic dye. The procedure is found to be easy, practical, safely and reliable

Experimental and numerical investigation of air blast mitigation of single and multi-scale structures

In order to protect civilians and infrastructure against the damaging effects of explosions, understanding blast wave interactions with structures in complex environments is fundamental for effective blast mitigation development. Obstructing the direct propagation of blast waves towards targets using a small, porous structure formed as an array/matrix of smaller structural elements is usually a preferred protective strategy in urban environments due to issues related to sustainability including material use and public perceptions of hazard. The blast wave mitigation induced by interaction with obstacles in downstream region is primarily dominated by configuration- shapes and lengths of individual elements- of the obstacle itself. Whilst the blast wave mitigation behaviour of obstacles arranged as an array/matrix comprising single-length scale and regular shape is well known, the mitigation behaviour of obstacles arranged as fractals involving multi-scale length and self-similarity features is not clear yet. The primary aim of this thesis was to extensively understand the blast mitigation behaviour of fractal obstacles of increasing complexity for developing protection strategies and predictive methods. To achieve this, an experiment on blast wave interaction with fractal obstacles was conducted to measure the blast attenuation and observe the mitigation behaviour. CFD numerical models simulating air blast loading in free-field and complex interaction scenarios were validated against experimental data. Utilising the validated numerical models, the mitigation behaviour of blast loading through blast-obstacle interactions process was studied for single obstacle case, and fractal obstacles with increasing complexity scenarios. The experimental findings exhibited that obstacles with shapes closely resembling true fractals can induce local significant blast attenuation up to 26\% in pressure and 16\% in peak specific impulse attributed to a mechanism known as trapping. This indicated that the mechanism of blast mitigation of fractal obstacles of increasing complexity is fundamentally different from singular or arrays of regular obstacles. Furthermore, blast wave parameters behind different arrangements of fractal obstacles were found to be inherently determinable. The numerical simulations revealed that the development of a complex flow-field downstream is comprised of two zones: wave shadowing and wave interference in which mitigation patterns, specifically behind the single obstacle, can be predictable despite the complex interactions. It was also shown that increasing the fractal obstacles complexity can produce a better impedance and substantially alter the direction of the incident wave. This has demonstrated that the effectiveness of obstructing a blast wave, measured in terms of blast intensity mitigation, is classified according to the fractal complexity configuration from the lowest level to the highest level. The peak reduction in pressure and specific impulse in the downstream region of fractal obstacle with highest level of complexity was numerically found to be 60\% and 40\% respectively. Therefore, the finding of this can be utilised in structural design and optimization of protective structures with improved blast mitigation

Natural Oil Nanoemulsion-Based Gel Vehicle for Enhancing Antifungal Effect of Topical Luliconazole

Background: Luliconazole, a newer class of imidazole anti-fungal agent, is very effective against several species of fungi, especially dermatophytes. It has very low aqueous solubility acting as barrier for topical delivery and limiting its dermal availability. Aim of the study: This study aimed to formulate luliconazole oil/water nanoemulsion by the aqueous titration method. Methods: Solubility study resulted in selecting peppermint oil, tween 80 and transcutol p as oil phase, surfactant and cosurfactant respectively, although pseudoternary phase diagram construct nanoemulsion area for picking formulations. Fifteen o/w nanoemulsion formulations prepared and characterised for droplet size, polydispersity index, pH values, percent transmittance, luliconazole content. Among formulations, eight preparations introduced to enhance the viscosity of prepared nanoemulsion by combining 0.5% carbopol 934 as gelling agent. Results: The selected preparations demonstrated homogeneous nanoemulgels with pH values appropriate for skin application and accepted luliconazole content. Viscosity results manifested non-newtonian pseudo plastic behavior with shear-thinning viscosity profile. In vitro release studies revealed dissimilar release profile (f2˂50) than that of pure luliconazole dispersion. The results revealed that the formula NG-1 with oil: Smix(2:1):water (15:40:43.5) ratio containing 1% drug and 0.5% carbopol 934 was the optimised formula with excellent spreadability. Conclusion: The study concluded that nanoemulsion-based gel is contemplated an encouraging and proceed technique for the topical preparation and upgrade solubility, dissolution rate and permeability of insufficient water-soluble drugs across the skin

Combination of FDM 3D Printing and Compressed Tablet for Preparation of Baclofen as Gastro-Floating Drug Delivery System (Conference Paper )#

This study aimed to develop an oral drug delivery system for gastro-retentive sustained drug release of baclofen by using a 3D printed capsular device since baclofen has a short half-life of 2.5 to 4 hours and has a narrow absorption window. Firstly sustained-release tablets of baclofen were formulated through the hot-melt extrusion of various thermoplastic polymers and direct compression of the extrudate, then a capsular device was designed and 3D printed to contain two air pockets to enable floating of the device and has four windows for drug release. 3D printing of the capsular device was done by an FDM printer using biodegradable PLA filament, and the sustained release tablets were inserted into the device to allow the medicine to be released into the stomach over a longer period. An in vitro buoyance test and an in vitro dissolution test were used to examine the buoyancy and sustained-release features of the formulated gastro-floating system. Five sustained release formulas were developed using different thermoplastic polymers in hot-melt extrusion. Produced tablets were assayed for drug content, hardness, and friability while a DSC study was done on the selected formula. F 5 which contains 20% baclofen, 55% Eudragit RS-100, 20% ethylcellulose, and 5% PEG 4000 showed sustained release where the complete dissolution of the drug occurred in 12 hours, and the gastro-floating device remained floating all the time. This method has a great potential for developing various floating drug delivery systems with the required release profile

New insight into single phase formation of capric acid/menthol eutectic mixtures by Fourier-transform infrared spectroscopy and differential scanning calorimetry

Purpose: To examine the structural changes of a eutectic mixture comprising capric acid and menthol which are commonly used in pharmaceutical applications. Methods: A phase diagram was constructed by quantitative mixing of capric acid and menthol under controlled conditions until a single liquid phase was formed. Eutectic mixtures of capric acid: menthol at the ratios of 3:2, 1:4, 1:1, 2:3, and 1:4 were prepared. Hydrogen bond formation and conformational changes were analyzed using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Microscopic imaging was carried out to capture phase change events upon increasing temperature. Results: Menthol confirmed the intact structure of a hexagonal ring. The high degree of broadening of the menthol O-H groups indicates hydrogen bond formation. FTIR band changes related to capric acid suggest a break-up of the methylene arrangement structure due to changes in the C-H band frequencies. The red shift encountered in C=O stretching band emphasizes hydrogen bond formation taking place between the oxygen atom of the hydroxyl group comprising the carboxylic moiety of capric acid and the hydrogen atom of menthol hydroxyl group. DSC results indicate the presence of two polymorphs of the capric acid/ menthol complex. Both exhibited crystallization and conformational change exotherms in addition to two melting endotherms as result of transformation of crystalline components to become partially crystalline due to hydrogen bond formation. Conclusion: The interaction between capric acid and menthol results in a typical preparation of deep eutectic systems that can act as natural-based solvents in numerous pharmaceutical applications. Keywords: Eutectic system, Capric acid, Menthol, Differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTI

THE POTENTIAL IMPACTS OF THE ANTI-EPILEPTIC DRUG (OXCARBAZEPINE) ON ALBINO RAT'S NEONATES DURING LACTATION

ABSTRACT Objective: This study was undertaken to evaluate the potential risks of the anti-epileptic drug (oxcarbazepine [OXC]) administration on neonates. Methods: The nursing rats orally administered from 7 th day of gestation until the 28 day of lactation with 108 mg/kg OXC (human equivalent dose) daily. The neonates at day 7, 14, 21, and 28 of lactation were sacrificed and the postnatal developmental signs and skeletal malformation and the histopathology of liver, kidney, and brain of the pups were examined. th Results: Our results showed that OXC induced a significant reduction in the neonatal weight and length, delayed, weak and incomplete ossification, wavy ribs and the neonatal liver revealed histopathological changes, pyknotic hepatocytes, cytoplasmic vacuolization, dilated sinusoid, and necrotic area. Kidney revealed alternation changes, enlargement of the glomerulus, renal tubules degeneration, and lymphatic infiltration. Brain (cerebral cortex and cerebellum) showed neurodegenerative changes, vacuolization of neuropil, congested and dilated blood vessel and dark stain neurons. Biochemical studies showed that OXC induced a reduction in the level glutathione reduced an important intracellular antioxidant, and catalase (enzymatic antioxidant) compared to control group. Conclusions: We support and proof the potential risks of the OXC administration on neonates. Keywords: Rats, Lactation, Oxcarbazepine, Antiepileptic drug

Enhancement of the Solubility and Dissolution Rate of Rebamipide by Using Solid Dispersion Technique (Part I)

Solid dispersion is an attractive tool of pharmaceutical technology used to improve the physical properties of drugs. Among these properties is to enhance the solubility of the drugs. Rebamipide is a poorly soluble drug of class IV of biopharmaceutical classification system (BCS). Rebamipide is used as potent antiulcer, mucoprotective drug, by stimulating the generation of prostoglandine enhanced mucosal protection. Rebamipide was formulated as a solid dispersion using different polymers such as pluronic F-127, PEG6000, PVP K30, and TPGS by using different preparation methods solvent evaporation, fusion, and kneading methods. It was seen that rebamipide was successfully dispersed in a homogenous solid dispersion matrix by solvent evaporation method using TPGS (1:15) drug carrier ratio. Moreover, the results revealed that the solubility of rebamipide (23.9µg/ml) increased significantly (p?0.05) by 36.4 x fold to obtain 874µg/ml solubility in rebamipide matrix. On the other hand, characterization of rebamipide solid dispersion using FTIR, DSC, SEM and x-ray diffraction demonstrated no drug polymer interaction, and converting the rebamipide from crystal to amorphous state lattice

Investigation of Solubility Enhancement Approaches of Ticagrelor

ABSTRACT                    Ticagrelor is an orally administered antiplatelet medicine, direct-acting P2Y12-receptor antagonist. Ticagrelor binds reversibly and noncompetitively to the P2Y12 receptor at a site distinct from that of the endogenous agonist adenosine diphosphate (ADP). Inhibition of platelet aggregation stimulated by ADP is a commonly used pharmacodynamic parameter for P2Y12-receptor antagonists.                   Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10?g/mL at room temperature. Ticagrelor exhibits no pKa value within the physiological range. Ticagrelor does not exhibit pH-dependent solubility and is defined as ‘low solubility low permeability’ under the Biopharmaceutics Classification System (Class IV). The mean absolute bioavailability of ticagrelor in healthy volunteers is 36 %                    Nanoparticles preparation and complexation is one of the recently used approaches to enhance the solubility of drugs. The aim of the present work was to improve the solubility and dissolution of ticagrelor by preparing nanoparticles and cyclodextrin inclusion complex of ticagrelor and then incorporated in to tablet dosage form. Fifteen formulas of nanoparticles were prepared by antisolvent precipitation method (solvent displacement method) utilizing one of the three polymers (PVP, Poloxamer, and HPMC) at three different drugs: polymer and solvent: anti-solvent ratios and nine formulas of cyclodextrin inclusion complex with HP?CD  by three preparation methods, physical trituration, kneading and solvent evaporation, which increase the solubility and dissolution rate of ticagrelor via formation of inclusion complex with HP?CD.               The prepared formulas were characterized regarding the saturated solubility, polydispersity index, particle size by nano laser particle size analyzer, % yield, entrapment efficiency, and flowability, FTIR, DSC, and SEM. The selected formulas were prepared as tablets.              The prepared tablets were evaluated for drug content, weight variation, hardness, and friability. In vitro dissolution data of the prepared tablets were analyzed using similarity factor (f2) and dissolution efficiency (DE).              Among all the prepared nanoparticles formulas, formula (F12) which contain HPMC as a polymer at polymer: drug ratio of (1:1) and solvent: antisolvent ratio of (1:1) was considered as the optimum formula which shows good evaluation parameters in addition to the increment in the solubility to about 9 times than that of the pure drug. The nanoparticle of the selected formula (F12) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 88 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  Moreover, the analysis by DSC and SEM of the nanoparticles of the selected formula (F12) indicate a reduction in the crystallinity and amorphization of the drug. It can be concluded that the selected formula is a promising formula for the preparation of ticagrelor nanoparticles the incorporation in a tablet dosage form.           Regarding ticagrelor inclusion complex with HP?CD Solvent evaporation method was the most effective method regarding ticagrelor solubilization and optimum formula of inclusion complex (F23) show increment in saturated solubility about ten times that of pure drug.           The ticagrelor inclusion complex of the selected formula (F23) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 90 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).