Controlled release systems based on natural lipid beeswax and loaded with Niflumic acid (NA) or inclusion complexes of NA with β-cyclodextrin are developed with the aim of simultaneously increasing the drug solubilisation, reducing the gastric side effects, and controlling the drug release. Simple and Green methods are used; firstly, the inclusion complexes of NA:b-CD (1:1) are prepared by physical grinding, co-evaporation, and co-precipitation. Secondly, the beeswax microspheres are elaborated by the hot-melt technique of microencapsulation using three emulsifying agents: PVA, Tween 20, and Tween 80. The formulations are analysed by FTIR, XRD, DSC, SEM, and optical microscopy. Depending on the complex type and surfactant agent, microencapsulation efficacy ranged from 50 to 96%. The in-vitro drug dissolution study in acidic fluid at pH = 1.2 and 37 °C showed different release profiles. So, the effect of surfactant is highlighted, and a remarkable efficacy of the combination of inclusion complex and microencapsulation using beeswax is perceived for simultaneously increasing the drug solubility and controlling the drug release. KEY WORDS: Beeswax, Niflumic acid, b-Cyclodextrin inclusion complex, Microencapsulation, Drug delivery Bull. Chem. Soc. Ethiop. 2026, 40(10), 2237-2253. DOI: https://dx.doi.org/10.4314/bcse.v40i10.13

Metronidazole (MET) is an effective agent known for its antibacterial and antiprotozoal activities. It can be administered by oral, intravenous, and topical routes, and its efficacy has been proven for the treatment of a large range of infections, including gastrointestinal diseases. MET is classified as a highly soluble and highly permeable drug; therefore, this study presents a novel sequential ethylcellulose–beeswax coating strategy for the preparation of metronidazole-loaded particles, combining a cellulose derivative matrix with a lipid outer layer to improve the encapsulation efficacy and modulate the drug release. Firstly, ethylcellulose (EC) nanoparticles are prepared using the water-in-oil emulsion solvent evaporation process of microencapsulation. Secondly, the obtained nanoparticles are coated with beeswax (BW), a natural wall material that offers gastro-resistant and therapeutic benefits, via a hot-melt process of microencapsulation. The encapsulation procedure is conducted following factorial designs, and the obtained formulations characteristics are examined using several techniques. The effects of some variables, namely MET:EC and (MET:EC):BW ratios and stirring speed, on the drug content and the number mean diameter (d10) are investigated by modeling using DOE-Minitab software. The Metronidazole release from all formulations is carried out in three fluids with pH = 1.2, 6.5, and 8.5 at 37 °C. Different kinetic models i.e., zero order, first order, Hixson-Crowell, Higuchi and korsmeyer-Peppas models, are tested to identify the drug release mechanism.

Mefenamic acid (MA) is one of the low water soluble non-steroidal anti inflammatory drugs (NSAID), exhibiting poor wetting and poor dissolution. MA forms with β-cyclodextrin supramolecular inclusion complexes approving a drug solubility enhancement. The aim of the study is to combine the solubilization capability of a supramolecule MA:b-CD with the complementary functional properties of Ethylcellulose (EC) and hydroxylpropylmethylcellulose (HPMC) hybrid coat for the development of new MA controlled drug delivery systems, by using emulsion-solvent evaporation technique. First, a 22 factorial design is drawn to prepare and optimize pure MA/HPMC:EC microspheres, by studying and evaluating the effect of HPMC:EC ratio (1:1 and 1:4) and stirring speed of emulsion (600 and 1000 rpm) on the drug entrapment. The results showed that the main effect of variables is statistically significant, the drug entrapment was improved using HPMC and varied from 20 to 39%. Second, MA:b-CD inclusion complex was prepared by solvent co-evaporation method and subsequently encapsulated into EC and EC/HPMC hybrid matrices. The in vitro drug dissolution tests were performed in phosphate buffer solution with pH=7.4 at 37°C and the results showed that the drug release was effectively increased for MA:b-CD inclusion complex loaded microspheres.

Beeswax is selected as a natural coating material for the development of new colon specific drug delivery systems charged by mesalamine. In a first step, beeswax microparticles are prepared using hot -melt process of microencapsulation where drug:beeswax ratio, stirring speed, emulsifier concentration and pH of external phase are varied for the optimization of the drug entrapment and microparticles' morphology. The effect of the nature of the emulsifier is also discussed by studying the hydrophilic-lipophilic balance (HLB) value. In a second step, to obtain delayed delivery systems, bi-layered microspheres are elaborated by the process of emulsion-solvent evaporation using ethylcellulose or cellulose acetate butyrate as outer enteric coating layer. All formulations are characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy and optical microscopy. The drug release is established in simulated gastric, small bowel and colon liquids and the release mechanism is discussed by applying the Korsmeyer-Peppas model.

Preparation of microspheres containing Mesalazine referred to as 5-aminosalicylic acid (5-ASA) for colon targeting drug was carried out using the emulsion solvent evaporation technique. The formulation was based on 5ASA as the active agent, sodium Alginate (SA) andEthylcellulose (EC) as encapsulating agents, with polyvinyl alcohol (PVA) as emulsifier. The effects ofthe following processing parameters, 5-ASA %, EC:SA ratio and stirring rate on the properties of the resulting products in the form microspheres were considered. The samples were characterized using Optical microscopy, SEM, PXRD, FTIR, TGA, and DTG.In vitro release of 5-ASA from the different batches of microspheres was tested in biologically simulated fluids, (gastric; SGF, pH 1.2 for 2 h), then (intestinal fluid SIF, pH 7.4for 12 h) at 37 degrees C. The release kinetic results have been treated mathematically relaying on Higuchi's and Korsmeyer-Peppas' models for drug liberation. DOE study was performed to evaluate the interactive effects of variables on the drug entrapment and microparticle sizes. Molecular chemical interactions in structures were optimized using DFT analysis.

ABSTRACT. The objective of this work is to study the release of p-anisidine by the hydrolysis of synthesized Schiff bases N-vinylbenzylidene-p-anisidine (Im) as a monomer and its copolymers (Cp1, Cp2) with N,N-dimethylacrylamide (DMA). The hydrolysis behavior and kinetics are investigated in homogeneous media composed of ethanol/water (80% v/v) at 37 °C and at pH range of 4.0-10.0. The variation of the concentration over time is measured in thermostatically cells using UV-Vis spectroscopy. The results showed that the imine function hydrolysis obeyed to the first order for all compounds; the experimental kinetic constants are determined and the pH–rate diagram profile is established. It is noticed that the hydrolysis of imine function is extremely dependent on its carrier and the pH medium. KEY WORDS: p-Anisidine, Copolymer, Schiff base, Hydrolysis, pH–rate diagram, Controlled release Bull. Chem. Soc. Ethiop. 2023, 37(3), 745-755. DOI: https://dx.doi.org/10.4314/bcse.v37i3.16

The approach of the present paper is based on the study of methylene blue (MB) dye adsorption onto new biocomposite microspheres. The microparticles are composed of red wood powder and cellulose derivatives (ethylcellulose and cellulose acetate) and are prepared by emulsion-solvent evaporation process by varying some of the process parameters such as organic phase concentration (RW%), emulsifier concentration (PVA%) and stirring speed of emulsion (N). The obtained microparticles are characterized by infrared spectroscopy, X-ray diffraction, optical microscopy and scanning electron microscopy, the mean diameters of microparticles and pHpzc are also measured. Designs of experiments (DOE) are used for both the preparation and optimization of microparticles and MB removal study. The MB adsorption tests are carried out onto the optimized spherical microparticles with mean diameter (d32) of 321–334 µm where effects of selected variables i.e. RW%, temperature and MB initial concentration are analyzed and identified. Thus, statistical relationships between responses which are adsorption percentage (Ads. eq. %) and capacity (qe) at equilibrium and variables are determined. The results demonstrated synergistic effects of both RW% and MB initial concentration and an adversary effect of temperature on qe. The Ads.eq. % achieved 92% at a low MB initial concentration of 20 mg L−1.

Novel bio-composite films based on Algerian earth chestnut i.e. Bunium incrassatum roots (Talghouda, TG) and cellulose derivatives (ethylcellulose; EC and cellulose acetate; AC) are prepared and tested for methylene blue (MB) adsorption from aqueous solutions. The biomaterial films are elaborated by dissolution solvent evaporation technique and are characterized by infrared spectroscopy, X-ray diffraction, SEM and optical microscopy. The pH(pzc) is also determined. For the adsorption tests, design of experiments based on 2(3) factorial design is built and followed. So, the effects of TG:EC:AC ratio, pH and MB initial concentration are discussed on the basis of mathematical modelling using Minitab software. Mathematical relations between equilibrium adsorption percentages and capacities versus selected variables were obtained and illustrated by surface plots. The interactive effects between variables have been also identified. The results showed that the MB adsorption percentage exceeded 83% and is mostly affected by pH value. Nevertheless the adsorption capacity is affected by MB initial concentration.

The occurrence of dyes at a high concentration in water induces negative impacts on water ecosystem and harmful effects on human health. Among cationic dyes, methylene blue (MB) was largely studied and its removal from industrial wastewater via adsorption pathway has been widely investigated. This review will summarize the latest researches published over the past two years which discuss the removal of MB using cellulose-based films. The focus will be given on the synthesis, modification and preparation of cellulose-based films materials, and their performance on MB adsorption. The review is divided in two categories of cellulose-based films i.e. composite and bio-composite films.

L’acide niflumique est un anti-inflammatoires non steroidiens (AINS) d’une grande importance et presente une haute efficacite therapeutique vis-a-vis de certaines maladies.lessont prescrits dans des syndromes aigus, affections chroniques et rhumatismales. Ils sont connus par leurs proprietes analgesiques, anti-inflammatoires, antipyretiques, cardioprotecteurs…etc.Un nombre incontestable de travaux de recherche ont ete realises pour resoudre le problemedes effets secondaires de L’acide niflumiquetels que des troubles du systeme nerveux central, des troubles gastro-intestinaux,des reactions d'hypersensibilite, des troubles renaux / hepatiques, des reactions cutanees et la maniere d’y remedier est l’amelioration de son potentiel pharmacologique en modifiant ses proprietes et en variant les methodes et les procedes de formulation. Dans cet article, on va discuter et etudier certain travaux de recherche sur ce medicament a partir de l’annee 2010.

The aim of this study was to prepare and characterise inclusion complexes of a low water-soluble drug, mefenamic acid (MA), with β-cyclodextrin (β-CD). First, the phase solubility diagram of MA in β-CD was drawn from 0 to 21 × 10-3 M of β-CD concentration. A job's plot experiment was used to determine the stoichiometry of the MA:β-CD complex (2:1). The stability of this complex was confirmed by molecular modelling simulation. Three methods, namely solvent co-evaporation (CE), kneading (KN), and physical mixture (PM), were used to prepare the (2:1) MA:β-CD complexes. All complexes were fully characterised. The drug dissolution tests were established in simulated liquid gastric and the MA water solubility at pH 1.2 from complexes was significantly improved. The mechanism of MA released from the β-CD complexes was illustrated through a mathematical treatment. Finally, two in vitro experiments confirmed the interest to use a (2:1) MA:β-CD complex.

Microencapsulation is a technique used for the production of loaded drug micron-sized particles which permit to protect the drugs against environmental effects and to enhance their physicochemical properties and biological activity. Currently, the process becomes interesting in the most industrial fields, for that the choice of suitable carrier material is necessary to meet the needs of the industry. There by, this review is focused on a biological material used as coat matrix in microencapsulation processes which is beeswax. It covers some recent researches engaging the preparation of simple or composite beeswax microparticles as novel drug delivery systems in the pharmaceutical field.

The aim of this work is to investigate the solubility enhancement of mefenamic acid (MA), a non-steroidal anti-inflammatory agent, by formation of stable amorphous ternary system (MA, polyvinylpyrrolidone (PVP), β-cyclodextrin (β-CD)) compared to the binary system (MA, β-CD). Firstly, on the basis of the molecular docking simulation and job’s plot results, three methods were adopted for the preparation of the binary inclusion complexes at the ratio of 2:1 of MA:β-CD, namely solvent co-evaporation (CE), kneading (KN) and physical mixture (PM). However, in order to decrease tendency to self-assembly of cyclodextrins and form aggregates in aqueous media, each binary system was co-milled at ambient temperature in presence of different ratios of a highly water-soluble polymer (PVP). These complexes were characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), nuclear magnetic resonance (1H- and 13C-NMR) spectroscopy and scanning electron microscopy (SEM) techniques. The release of the drug from the diverse formulations was also investigated by means of UV-VIS spectroscopy. Finally anti-inflammatory and anti-nociceptive activities were performed. The results showed that the solubility of MA in water from ternary complexes was significantly improved.

The aim of this work is the enhancement of the hydrosolubility behaviour of a poorly soluble, weakly basic drug, using itraconazole (ITZ) as a case example. Binary inclusion complexes of ITZ with β-cyclodextrin (β-CD) are prepared in 1:2 molar ratios of ITZ to β-CD by co-evaporation method. Both solubility and dissolution behaviour are compared with that of the pure drug. Ternary complexes can be obtained by adding the polyvinylpirrolidone (PVP) which is a highly water soluble polymer, in the ITZ/ β-CD complex formation. Actually, Solid state analysis is performed for all formulations and for pure ITZ applying the Fourier transforms infrared (FT-IR) spectroscopy, powder X-ray diffraction (pX-RD) and differential scanning calorimetry (DSC). Solubility tests indicate that with all formulation, the solubility of ITZ formed with β-CD or β-CD and PVP proved to be increased. The obtained results show that the pure drug has a poor dissolution property, and the ternary inclusion complexes resulted in fast and extensive release of ITZ. Keywords: Itraconazole, β-cyclodextrin, polyvinylpyrrolidone.

Microparticles charged by niflumic acid and based on cellulose derivatives as polymeric matrices, that is, ethylcellulose (EC) and mixtures of EC and hydroxypropylmethylcellulose (HPMC), were elaborated using microencapsulation by emulsion-solvent evaporation technique. The niflumic acid is considered as a poorly water soluble drug, so the main objective of the paper is to use designs of experiment in order to prepare new solid formulations with a large range of size for the drug dissolution enhancement. The possible drug-polymer interaction was investigated by Fourier transform-infrared spectroscopy, X-ray diffraction, and differential scanning calorimetric analysis. Some of the process variables, namely, the stirring speed of emulsion, the emulsifier concentration, and the EC:HPMC ratio, were selected and varied. Their main and interactive effects on the microparticles' characteristics were obviously evaluated and discussed using Minitab software 16.1. The obtained microparticles' size (d(10)) ranged from 196 to 796 mu m, and the drug entrapment reached 45% in some formulations. The drug dissolution results showed that the Higuchi's release constant varied from 0.011 to 0.067 min(-1/2) and was enhanced especially when the HPMC concentration was increased.

In the present paper, factorial designs of experiments (DOE) were built in the aim of preparing new solid optimized controlled release microparticles charged with the herbicide 2,4-D and, also investigating the influence of some process and encapsulation variables. Composed from mixtures of ethylcellulose (EC) / hydroxy propyl methyl cellulose (HPMC), cellulose acetate butyrate butyryle (CAB) / HPMC and pure CAB as biodegradable polymeric matrices, the microparticles were prepared by emulsification-solvent evaporation technique. Then, the effect of some parameters such as the stirring speed of emulsification, initial drug concentration and polymer concentration were studied. Depending on the selected variables, a large range of microparticles’ size was obtained; from 25 to 208 µm of d 10 and the 2,4-D content reached 69%. Also, different release profiles accompanied with a burst effect were obtained. Finaly, by modelling using Minitab 16.1 software, the main and interactive effects of these variables on the microparticles’ chacteristics (size, drug entrapment and drug release) were evaluated.

Purpose: The present study is intended to the preparation and optimization of controlled drug release microparticles based on polylactic acid and Mesalazine. This active ingredient is usually used in the therapy of intestine inflammatory diseases, particularly the Crohn's disease and hemorrhagic recto colitis. Methods: Microencapsulation by simple O/W emulsion solvent evaporation method was used to prepare these formulations. Some of the process variables such as the emulsifier concentration, the polymer concentration, the drug: polymer ratio and stirring speed were varied and the obtained biodegradable microparticles were characterized by FTIR spectroscopy, X-ray diffraction, DSC method and optical microscopy. The drug release was established both in simulated intestinal fluid and distilled water and the data analysis and the release mechanism were investigated on the basis of Higuchi and Korsmeyer-Peppas models. Results: The microparticles' size i.e. the number mean diameter (d10) ranged from 127 to 744 mu m and the drug content varied from 12 to 27%. The effect of the selected variables on the microparticles' characteristics (size, morphology and drug release) were exhaustively discussed for the PLA/mesalazine microparticles' optimization. Conclusion: This study showed that the microparticles' morphology depended strongly on the emulsifier concentration and the drug entrapment is related to the initial drug: polymer ratio and polymer concentration.

New formulations capable to enhance piroxicam (PRX) water solubility and at the same time to control and adjust its release have been developed. For this purpose, two methods have been used and combined to achieve this goal, namely complexation and microencapsulation by O/W emulsion solvent evaporation. In order to modify the drug release, first, microparticles composed of pure PRX and ethylcellulose (EC) or mixtures of EC and hydroxypropylmethylcellulose (HPMC) were prepared, and then, other micropaticles containing the β-cyclodextrin/piroxicam (β-CD/PRX) complex obtained by the solvent evaporation technique and EC or a mixture of EC and HPMC were produced and tested. These formulations were characterized by FT-IR, XRD, optical microscopy, and SEM methods. Drug dissolution tests were carried out in acidic media at pH = 1.2 and 37°C. Depending on the microparticles composition, their size ( d 10 ) ranged between 49 μ.m and 121 μ.m and PRX loaded varied from 10.8 % to 27.7 %. The effect of complexation and HPMC polymer on the drug release was investigated; the results demonstrated that the Higuchi’s release constant significantly increased when using the EC/HPMC mixture as a matrix with pure PRX or only EC as a matrix with the β -CD/PRX complex. The results are remarkably promising since the combination of these processes provided new SD-CR formulations of piroxicam which enabled simultaneous enhancement and control of its release from the carriers.

The present paper is devoted to the study of the non-steroidal anti-inflammatory niflumic acid (NA) release from dosage forms in simulated gastric and intestinal liquids (pH=1.2 and 6.8). New formulations (tablets) based on native, pregelatinized and cross-linked (DSA) corn starches were developed and tested. The proposed matrices were used in order to modify the NA release and especially to reduce its gastrointestinal side effect. The cross-linked matrix i.e. distarch adipate (DSA) was obtained by chemical modification of native starch using adipic acid/acetic anhydride. The different starches were characterized by different methods (FTIR, X-ray, swelling power). As well, the effects of the matrix and its concentration on the drug release from tablets were investigated. Finally different mathematical models i.e. zero and first order, Higuchi and Korsmeyer–Peppas models were tested in order to evaluate the release mechanism.