Pharmaceutical Microemulsions Research Articles

Exploring Microfluidic Platform Technique for Continuous Production of Pharmaceutical Microemulsions

Objective of present work was to develop microfluidic-based technique for continuous production of drug (luliconazole)-loaded microemulsion. Pseudo-ternary phase diagrams were constructed, and optimization of concentration of selected formulation components like Capmul MCM, Tween 20 and Transcutol P was done using the Box-Behnken design (BBD). Batch process and microfluidic process were compared in terms of droplet size. Further, microemulsion was loaded into chitosan-based gel, and ex vivo skin permeation study was carried in comparison with marketed formulation. Optimized batch (ME 1) with Capmul MCM (10% v/v) and mixture of Tween 20 and Transcutol P (32.5% v/v) processed with flow rate of 20 mL/min through microfluidic device exhibited droplet size of 24.9 ± 3 nm (PDI 0.4 ± 0.03). Developed formulation enhanced flux of luliconazole across skin and was stable for 3 months. Increase in volume (20 to 100 mL) for batch process led to corresponding increment in droplet size (from 31.1 ± 11.9 to 56.4 nm) indicating lack of uniformity. Alternatively, for microfluidic device, such alterations in droplet size were avoided. Achievement of prerequisite droplet size is imperative to colloidal stability of microemulsions and is problematic at larger batch sizes. Batch processes employed are unable to address major issue of uniformity in droplet size and ease of scale up. Experimental findings conclude that as opposed to bath processes, consistent production of microemulsion would be achieved even with higher batch size using microfluidic device. Results strongly advocate further exploration of microfluidic platforms for producing drug-loaded microemulsions.

DEVELOPMENT AND VALIDATION OF A SIMPLE HPLC METHOD FOR ESTIMATION OF MYCOPHENOLATE MOFETIL IN MICROEMULSION FORMULATION

Objective: The present study deals with the development, validation and application of a simple, precise and accurate HPLC method for the determination of mycophenolate mofetil in pharmaceutical formulations and microemulsions.
 Methods: In this method, a simple isocratic mobile phase composition of methanol and water (75:25 v/v) pumped at 1 ml/minute flow rate through Phenomenex C18 column (dimension: 250 4.6 mm and 5 µm particle size) was used. Injection volume was 20 µl and analysis of mycophenolate mofetil was carried out at 250 nm.
 Results: The coefficient of regression was found to be 0.9996, indicating the linearity of the developed method within a range of 0.1 to 10 µg/ml. The limit of detection (LOD) and the limit of quantization (LOQ) were found to be 3.660ng/ml and 11.091ng/ml, respectively. The results showed that % deviation for change in compositions of the mobile phase, flow rate and temperature was within a range of-5.51 to 10.99%,-3.70 to 8.80% and-5.29 to 10.90%, respectively. The method seemed sensitive to change of temperature (±5 ○C) and methanol composition (±2%) as the results were at the boundary limit of 10% deviation.
 Conclusion: A simple, precise and accurate HPLC method for the determination of drug content from microemulsion has been developed and validated in accordance with ICH guidelines.

MesoDyn prediction of a pharmaceutical microemulsion self-assembly consistent with experimental measurements

In this work, for the first time a coarse-grained model in a mesoscopic dynamic (MesoDyn) simulation for a pharmaceutical nonionic surfactant Brij97 was presented. By using this coarse-grained model, the morphology transition from oil in water (O/W) to a bicontinuous microemulsion formed in the Brij97/isopropanol/isoamyl acetate/H2O quaternary system was predicted. Furthermore, the effect of emulsifier/isoamyl acetate mass ratio, Brij97/alcohol mass ratio and alcohol structure on the droplets size and kinetic formation process of the O/W microemulsion were studied. These MesoDyn predictions were consistent with experimental measurements. This makes it possible to further predict the formation mechanism of complex drug-loaded aggregates of Brij97 by using this coarse-grained model.

Formulation aspects behind the development of a stable biphasic liquid dosage form with special reference to microemulsion

Biphasic liquid dosage have an associated limitation of poor physical stability and therefore it is said to be thermodynamically unstable. Moreover, this area is also of great interest among the researchers towards the improvement of the stability. Thus, development of microemulsion systems is of great interest among the researchers. A microemulsion is a system of water, oil and amphiphilic compounds (surfactant and co-surfactant) which is a transparent, single opticalisotropic and thermodynamical stable liquid. Microemulsions are readily distinguished from normal emulsions by their transparency, low viscosity and more fundamentally their thermodynamic stability. In this review article, the various aspects of pharmaceutical microemulsion were compiled together and the target audiences are specifically the M. Pharm and B. Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

Pharmaceutical Considerations behind the Development and Evaluation of Mucoadhesive Tablets

The current article has been focused on the Mucoadhesive drug delivery system may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The Mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, Mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various Mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal) based on literatures were reported so far. In this review article, the various aspects of pharmaceutical microemulsion were compiled together and the target audiences are specifically the M. Pharm and B. Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

Microemulsion formulation of Carbendazim and its in vitro antifungal activities evaluation.

The fungus Rhizoctonia solani Kuhn is a widespread and destructive plant pathogen with a very broad host range. Although various pathogens, including R. solani, have been traditionally controlled using chemical pesticides, their use faces drawbacks such as environmental pollution, development of pesticide resistance, and other negative effects. Carbendazim is a well-known antifungal agent capable of controlling a broad range of plant diseases, but its use is hampered by its poor aqueous solubility. In this study, we describe an environmentally friendly pharmaceutical microemulsion system using carbendazim as the active ingredient, chloroform and acetic acid as solvents, and the surfactants HSH and 0204 as emulsifiers. This system increased the solubility of carbendazim to 30 g/L. The optimal microemulsion formulation was determined based on a pseudo-ternary phase diagram; its physicochemical characteristics were also tested. The cloud point was greater than 90°C and it was resistant to freezing down to −18°C, both of which are improvements over the temperature range in which pure carbendazim can be used. This microemulsion meets the standard for pesticide microemulsions and demonstrated better activity against R. solani AG1-IA, relative to an aqueous solution of pure carbendazim (0.2 g/L). The mechanism of activity was reflected in the inhibition of against R. solani AG1-IA including mycelium growth, and sclerotia formation and germination were significantly better than that of 0.2 g/L carbendazim water solution according to the results of t-test done by SPSS 19.

Water solubilization capacity of pharmaceutical microemulsions based on Peceol®, lecithin and ethanol

Biocompatible microemulsions composed of Peceol®, lecithin, ethanol and water developed for encapsulation of hydrophilic drugs were investigated. The binary mixture Peceol®/ethanol was studied first. It was shown that the addition of ethanol to pure Peceol® has a significant fluidifying and disordering effect on the Peceol® supramolecular structure with an enhancement in water solubilization. The water solubilization capacity was improved by adding lecithin as a third component. It was then demonstrated that the ethanol/lecithin weight ratio played an important role in determining the optimal composition in term of water solubilization efficiency, a necessary property for a nutraceutical or pharmaceutical application. The optimal ethanol/lecithin weight ratio in the Peceol® rich region was found to be 40/60. Combination different techniques such as SAXS, fluorimetry, rheology and conductivity, we analyzed the water uptake within the microemulsion taking into account the partitioning of ethanol between polar and apolar domains. This ethanol distribution quantified along a water dilution line has a major effect on microemulsion properties.

Antimicrobial Mechanism Analysis of an Oil in Water Microemulsion by DNA Microarray-Mediated Transcriptional Profiling ofEscherichia Coli

The DNA microarray was employed in this study to investigate the gene expression profiles of Escherichia coli treated by oil in water (o/w) microemulsion in order to better understand the antimicrobial mechanism of the microemulsion as a promising food-grade antimicrobial system. Among 5,440 open reading frames of E. coli, a total of 634 and 501 were highly induced and repressed, respectively. According to the annotation and analysis in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, it was found that the differently expressed genes were mainly involved in the biosynthesis of cell wall components and membranes, phosphate-related metabolism and some other biosynthetic pathways, suggesting that the main antibacterial mechanisms of the o/w microemulsion were the attacks to the cell surface structure, especially the cell wall, and its influences on the metabolism of phosphate of the E. coli cells through phosphate absorption inhibition. Practical Applications In the panorama of the increasing need to search for novel strategies in order to prevent foodborne outbreaks, microemulsion systems have been of great interest to researchers for their broad antimicrobial properties. In our group, a series of food-grade or pharmaceutical microemulsion systems based on glycerol monolaurate have been established for antimicrobial applications. It was found that the prepared microemulsions possessed excellent broad-spectrum antimicrobial activities due to the disruption and dysfunction of biological membranes and cell walls, as suggested by the transmission electron microscopy observations and membrane permeability experiments. The antimicrobial mechanisms analysis of the microemulsion mediated by DNA microarray in this work will be of great importance in exploring the structure–activity relationship of the o/w microemulsion at molecular biological levels in future work, in order to provide a guideline in designing food-grade antimicrobial microemulsions.

Characterization and antimicrobial activity of a pharmaceutical microemulsion

The characterization of a pharmaceutical microemulsion system with glycerol monolaurate as oil, ethanol as cosurfactant, Tween 40 as surfactant, sodium diacetate and water, and the antimicrobial activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Aspergillus niger and Penicillium expansum have been studied. The influence of ethanol and sodium diacetate on oil solubilization capability was clearly reflected in the phase behavior of these systems. One microemulsion formulation was obtained and remained stable by physical stability studies. The antimicrobial assay using solid medium diffusion method showed that the prepared microemulsion was comparable to the commonly used antimicrobials as positive controls. The kinetics of killing experiments demonstrated that the microemulsion caused a complete loss of viability of bacterial cells ( E. coli, S. aureus and B. subtilis) in 1 min, killed over 99% A. niger and P. expansum spores and 99.9% C. albicans cells rapidly within 2 min and resulted in a complete loss of fungal viability in 5 min. The fast killing kinetics of the microemulsion was in good agreement with the transmission electron microscopy observations, indicating the antimembrane activity of the microemulsion on bacterial and fungal cells due to the disruption and dysfunction of biological membranes and cell walls.

The influence of cosurfactants and oils on the formation of pharmaceutical microemulsions based on PEG-8 caprylic/capric glycerides

In the present study the effect of type and concentration of a cosurfactant and oil on the ability of nonionic surfactant PEG-8 caprylic/capric glycerides (Labrasol ®) to solubilize both oil and water phases was evaluated. Seven different cosurfactants (polyglyceryl-6 dioleate (Plurol Oleique ®) (PO), polyglyceryl-6 isostearate (Plurol Isostearique ®) (PI), polyglyceryl-4 isostearate (Isolan ® GI 34) (IGI34), octoxynol-12 (and) polysorbate 20 (Solubilisant gamma ® 2421) (SG2421), octoxynol-12 (and) polysorbate 20 (and) PEG-40 hydrogenated castor oil (Solubilisant gamma ® 2429) (SG2429), PEG-40 hydrogenated castor oil (Cremophor ® RH 40) (CRH40) and diethyleneglycol monoethyl ether (Transcutol ®)) and six oils (isopropyl myristate, ethyl oleate, decyl oleate, medium chain triglycerides, mineral oil and olive oil) were used in phase behaviour studies of a quaternary system Labrasol ®/cosurfactant/oil/water. The amount of surfactant required to completely homogenize equal masses of oil and water to form a single phase microemulsion (termed as balanced microemulsion) (Smin, %w/w), the minimal concentration of the surfactant/cosurfactant blend required to produce a balanced microemulsion (SCoSmin, %w/w) as well as the maximum concentration of water solubilized in investigated surfactant/oil and surfactant/cosurfactant/oil mixtures ( W max, %w/w) were determined. The obtained results indicated that Labrasol ® showed a good efficiency in the presence of lower molecular volume fatty acid esters with a preferred chemical structure such as isopropyl myristate (Smin 56.14% (w/w); W max 12.28% (w/w)). Oils with high molecular volume (olive oil and mineral oil) do not result in microemulsion formation. Transcutol ® decreased the capacity of Labrasol ® for solubilization of oil and water phases. The tendency of Labrasol ® to solubilize both, water and oil phases, was favoured by polyglycerol-6 ester type of cosurfactants (PO and PI) while the influence of the polyglycerol-4 ester (IGI34) as well as of polyoxyethylene type of cosurfactants (CRH40, SG2421 and SG2429) on the surfactant efficiency, was not significant. Furthermore, the results revealed the significant influence of the surfactant/cosurfactant mass ratio ( K m) on synergistic effect between polyglyceryl-6 esters and Labrasol ® in the formation of microemulsions using isopropyl myristate as oil phase. Optimized microemulsion systems were stabilized with Labrasol ®/polyglyceryl-6 esters blend at K m 5:5 (SCoSmin, 27.5% (w/w) and W max, 71.43% (w/w) for PI; SCoSmin, 29.18% (w/w) and W max, 65.00% (w/w) for PO) and the electrical conductivity measurement results for optimized balanced microemulsions showed that their structures were highly conductive indicating a bicontinuous microstructure.

New Pharmaceutical Microemulsion System for Encapsulation and Delivery of Diospyrin, a Plant-Derived Bioactive Quinonoid Compound

A new vegetable oil based oil-in-water microemulsion is developed and characterized as a prospective delivery system for in vivo application A particular weight percent composition 5/30/65 (clove oil/Tween-20/water) was selected (V1) from the clear oil-in-water zone of the pseudoternary phase diagram comprising clove oil, polyoxyethylene sorbitan monolaurate (Tween-20), and water. Two modifications of V1, (V2 and V3) were prepared by addition of dipalmitoyl phosphatidyl choline (DPPC), and a mixture of DPPC and cholesterol, respectively. A model drug diospyrin (a plantderived quinonoid compound) was encapsulated in the dispersed clove oil droplets of the three systems and designated as DV1, DV2, and DV3, respectively. The size of the dispersed clove oil droplets ranged between 9–20 nm as determined by dynamic light scattering. The stability of the vehicles, before and after encapsulation, was assessed under varying conditions of time and temperature and was found to be stable for 1 year and over a temperature range of 4-40°C. The ultraviolet-visible spectrum of diospyrin after encapsulation in the compartmentalized medium remained almost identical to that dissolved in chloroform. The single-dose acute toxicity of V1 and DV1 was assessed in vivo by carrying out survival study and enzyme assay in Swiss Albino mice.The vehicle was safe at a volume of 0.05 ml when injected intraperitoneally into the mice.

Microemulsões: estrutura e aplicações como sistema de liberação de fármacos

Depending on formula composition, microemulsions may be used as a vehicle for drug administration. In this work the main applicable parameters used in the development of pharmaceutical microemulsions (ME) are analyzed. The conceptual description of the system, theoretical parameters related to formation of internal phases and some aspects of ME stability are described. The pseudo ternary phase diagram is used to characterize ME boundaries and to describe different structures in several regions of the diagram. Some applications of ME as drug delivery systems for different administration routes are also analyzed. ME offer advantages as drug delivery systems, because they favor drug absorption, being in most cases faster and more efficient than other methods in delivering the same amount of drug.

Microemulsion of seal oil markedly enhances the transfer of a hydrophobic radiopharmaceutical into acetylated low density lipoprotein.

Four different microemulsions differing in their core lipid component (triolein, canola oil, squalene, or seal oil) and containing 1,3-dihydroxypropan-2-one 1,3-diiopanoate (DPIP), a potential radioimaging probe, were prepared by means of ultrasonication. The DPIP microemulsions were incubated with acetylated human low density lipoprotein (AcLDL) and the amount of DPIP transferred into AcLDL was examined. The amount of DPIP in the microemulsions expressed as DPIP/oil (w/w) was dependent on the core lipid component of the microemulsion in the order of seal oil (0.19+/-0.04, mean +/- standard deviation) > squalene (0.15+/-0.02) > canola oil (0.12+/-0.02) > triolein (0.07+/-0.004). With the exception of canola oil, all microemulsions were effective in enhancing the transfer of DPIP into AcLDL in comparison with commonly used methods, i.e., direct diffusion and detergent solubilization. DPIP in seal oil resulted in the highest amount of DPIP transferred into AcLDL [309.16+/-34.82 vs. 203.19+/-64.51 using squalene and 151.31+/-28.54 using triolein (DPIP molecules per AcLDL particle)]. For the first time, oil from harp seals, was studied as a major core lipid component of formulating pharmaceutical microemulsions. DPIP in seal oil resulted in the highest transfer of DPIP into AcLDL which is likely due to the highest DPIP concentration found in this microemulsion as well as the high fluidity of seal oil.

Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects.

This review highlights the state-of-the-art in pharmaceutical microemulsions with emphasis on self-emulsifying systems, from both a physical and biopharmaceutical perspective. Although these systems have several pharmaceutical applications, this review is primarily focused on their potential for oral drug delivery and intestinal absorption improvement. Physicochemical characteristics and formulation design based on drug solubility and membrane permeability are discussed. Case studies in which lipid microemulsions have successfully been used to improve drug solubilization/dissolution and/or intestinal absorption of poorly absorbed drugs/peptides are presented. Drug development issues such as commercial viability, mechanisms involved, range of applicability, safety, scale-up and manufacture are outlined, and future research and development efforts to address these issues are discussed.

Effect of oil chain length and electrolytes on water solubilization in alcohol-free pharmaceutical microemulsions

Effect of oil chain length and electrolytes on water solubilization in alcohol-free pharmaceutical microemulsions