Search

The skin is an attractive site for direct administration of drugs due to its easy access and patient compliance. The strategy in the development of a dermal pharmaceutical and a cosmetic product lies in a selection of suitable excipients capable of delivering the drug or active pharmaceutical ingredient at the site of its action. The key moment is overcoming the least permeable skin layer stratum corneum. Chemical penetration enhancers facilitate drug diffusion and accelerate drug delivery through the Stratum corneum, possibly in combination with hydration of the skin or increasing temperature. The paper summarises basic information about the most common chemical enhancers and the studies investigating the synergistic action of suitable combinations of chemical enhancers, which may also include microemulsions.

Mucoadhesive dosage forms, which are used for topical application in the oral cavity, are currently a very intensively developing field in pharmaceutical technology. Considering the physiological conditions of the oral cavity, the formulation of these mucoadhesive forms is still a challenge. Various types and forms of polymers are used in the experiments, in combination with a large number of drugs, while the achieved effect can be local or systemic and the release rate can be controlled. For many drugs, buccal application is one of the ways to increase their bioavailability.

There are several approaches for the formulation of abuse-deterrent, tamper-resistant, or alcohol-resistant dosage forms. This work is specifically focused on the formulation of microforms and multiple unit dosage forms with the mentioned resistant features. We prepared microcapsules based on sodium alginate by Ca2+-induced gelation, containing caffeine as a model drug. The prepared microcapsules were dried either by hot air or freeze-dried and the resistance in an alcoholic environment and the resistance against mechanical stress were observed. Subsequently, swelling studies were conducted to predict the behavior of prepared microcapsules during dissolution testing. Differences in the behavior of microcapsules during dissolution testing were strongly related to the different abilities of Ca2+-alginate microcapsules to swell in an acidic and alkaline environment. Alginate microcapsules exhibited gastro-resistant properties due to excellent swelling in an alkaline environment and poor swelling in a gastric environment. The addition of ethanol did not influence the swelling behavior of alginate microcapsules in the gastric fluid; rather, it showed the opposite effect, where swelling was slightly suppressed. Therefore, we conclude that alginate microcapsules are alcohol resistant. Also, they showed high mechanical strength, and therefore, grinding the microcapsules into a powder was impossible.

The pseudo-fruits of Dog Rose are a rich source of L-ascorbic acid and several other active substances, which means their high supportive therapeutic potential. The study aimed to examine the impact of the chosen technological procedure for the preparation of tablets containing rosehip powder on the amount of L-ascorbic acid in the final pharmaceutical form. Drying of the plant drug was performed at room temperature to avoid possible thermal degradation of this heat-sensitive compound. Similarly, drying of the granules after wet granulation in the oven was replaced by natural drying at room temperature. The composition of two types of prepared granule formulations differed in the filler – lactose (LAC) or microcrystalline cellulose (MCC). Apart from the disintegration test, they meet the technological requirements for granules or tablets. Lactose was confirmed as a more suitable filler, which despite the unsuccessful disintegration of the granules, ensures the disintegration of tablets within 15 minutes even without the addition of a special excipient acting as a disintegrant. The content of L-ascorbic acid detected using isotachophoresis – capillary zone electrophoresis was 87.16 ± 5.06 µg in LAC tablets and 63.33 ± 2.83 µg in MCC tablets.

Glyceryl laurate (GL) is a natural or synthetic surfactant with antiviral and antimicrobial activity and is not only effective in common colds or flu, but also against swine flu, herpes simplex, shingles, or chronic fatigue. The study aimed to formulate the GL granules as a semi-product for the compression of tablets and evaluate the influence of the substitution of sucrose laurate (Ryoto®) with sucrose ester (Sisterna®) in the composition of the granules and the effect of granule size on the quality of the compressed tablets. Four types of granules, varying in grain size and the type of additional surfactant, were prepared by melt granulation. The traditional pharmacopoeia tests were used to assess tablets’ quality. The granule size significantly affected all evaluated parameters: hardness, uniformity of mass, friability, and disintegration. The replacement of sucrose laurate with sucrose ester caused a slight decrease in tablet strength and a shortening of disintegration. However, it did not significantly impact friability and uniformity of mass. For this reason, the excipient, sucrose ester, can be evaluated as an adequate replacement in the composition of GL tablets.

During the development of medicinal forms (eye drops), it is necessary to consider several parameters, so that the medicine is nonirritating to the eye and, at the same time, has the desired effect. We prepared eye drops containing dexamethasone or its water-soluble salt in a 0.1% concentration. We compared suspension eye drops (with dexamethasone) and solution eye drops (with dexamethasone sodium phosphate) without viscosity adjustment as well as with viscosity adjustment by adding chitosan low molecular weight (LMW) with the mass-produced product Unidexa 1%. Acidity (pH), surface tension, density, viscosity, and irritability were evaluated. An in vitro or ex vivo test on human erythrocytes (red blood cells [RBCs]) was used to test irritability. Hemolysis of RBC was monitored by determining hemoglobin spectrophotometrically at a wavelength of 550 nm. The addition of chitosan 0.1% as a viscosity-increasing agent reduced the irritation potential of the experimental eye drops.

An important area of interest in pharmaceutical technology is the issue of poorly soluble drugs and their formulation into drug dosage forms that ensure optimal bioavailability. One of the options to solve solubility is the development of nanodispersion systems. This work is focused on the preparation of microemulsion systems suitable for poorly soluble drugs, for example, nimodipine. The composition and structure of microemulsion enable solubilization of different drugs and make it a universal drug carrier. Microemulsions increased the solubility of the model drug 20-fold compared to solubility in water. The use of mucoadhesive polymers – hydroxyethyl cellulose and xanthan gum – improved the in vitro release significantly. The highest amount of nimodipine was released from the microemulsion gel system with hydroxyethyl cellulose (1% w/w) and this depended on the diffusion of dissolved molecules.

Rectal administration is a suitable route of administration for drugs that are either very irritating to the intestine (e.g., indomethacin) or are more effective when the first-pass effect in the liver is circumvented. Microemulsions are a tool for the improvement of penetration of sparingly soluble drugs. They are mainly used in topical and transdermal drug delivery. However, they find application also in other routes of administration, mainly due to their ability to solubilize sparingly soluble drugs. The selection of a suppository base depends on the physical properties of the drug. The study focused on evaluating the effect of the microemulsion as the solubilizer of sparingly soluble indomethacin in hydrophilic and lipophilic suppository bases compared with Polysorbate 80 as the excipient contained in the microemulsion. The reference suppositories were prepared by the traditional moulding technique from Adeps solidus or Macrogol suppository base without the previous drug solubilization. The microemulsion-based suppositories were prepared after the initial solubilization of the drug in the microemulsion or Polysorbate 80, followed by the addition of suppository base to maintain the same drug/solubilizer ratio. The suppositories were tested for softening time, hardness, and uniformity of mass. The dissolution test was performed using the dialysis tubing method in the basket apparatus. The amount of indomethacin released into the dissolution medium was determined spectrophotometrically at 320 nm. The results indicate that solubilization of indomethacin in the microemulsion had a positive effect on in vitro drug release but not as significant as in the case of Polysorbate 80 used alone. The enhancement ratio for Polysorbate 80 in Adeps suppositories was 2.9, for the microemulsion in Adeps suppositories was 1.1, and for Polysorbate 80 in Macrogol suppositories was 7.4 after 3 hours. The test of uniformity of mass had shown that all suppositories (reference, solubilizer-containing) are within the permitted limits. The softening time was reduced by adding the solubilizer to each type of suppository base.

The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% ( w / w ) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen's egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions.

Background: Tretinoin (TRE) is, for its anti-comedogenic and comedolytic activity, widely used in the topical treatment of acne vulgaris. The effect lies in the regulation of sebum production and collagen synthesis. The study is devoted to the formulation of dermal gels containing TRE using microemulsion as the drug solubilizer., Methods: The aim was to evaluate the effect of the reference microemulsion (ME) and lecithin-containing microemulsion (ME L ) on the release of TRE through the synthetic membrane (in vitro) and the pig's ear skin (ex vivo) through the Franz cell diffusion method. Subsequently, after an ex vivo study, the amount of the drug in the skin influenced by the applied formulation was determined. In addition, the impact of ME on the microscopic structure, texture, and rheological properties of gels was evaluated., Results: On the basis of the analysis of texture, rheological properties, and drug release studies, Carbopol formulations appear to be more appropriate and stable. Considering the synthetic membrane as a stratum corneum , the Carbopol gel penetrated about 2.5-higher amounts of TRE compared to the Xanthan gel. In turn, ex vivo studies suggest that ME L slows the drug transfer to the dissolution medium, simulating absorption into the blood, which is a desirable effect in local treatment. The drug retention study proved the highest amounts of TRE in the skin to which microemulsion-Carbopol formulations were applied., Conclusion: The results confirm the benefit of TRE solubilization in ME due to its bioavailability from the tested dermal formulations.

This study aimed to prepare and evaluate pellets containing acyclovir as a model drug. Pellets were prepared by the extrusion-spheronization process. Aqueous solutions of natural marine polymers (sodium alginate, chitosan) were compared to semi-synthetic hydroxypropyl methylcellulose (HPMC) in the role of binders. The study focused on the characterization of the pellet properties that are crucial for the formulation of the final dosage form, such as in multi-unit pellet system (MUPS) tablets or hard gelatin capsules filled with the pellets. Finally, the mentioned dosage forms were tested for drug dissolution. The morphology of pellets observed by scanning electron microscopy correlated with the shape evaluation performed by dynamic image analysis. Sodium alginate pellets exhibited the lowest value of sphericity (0.93), and many elongated rods and dumbbells were observed in this batch. Chitosan pellets had the highest value of sphericity (0.97) and were also less rough on the surface. The pellets maintained a constant surface geometry during the dissolution studies; they only reduced in size. The most significant reduction in size and weight was assessed after 2 h of dissolution testing. This fact was in line with the drug release from pellets in capsules or MUPS tablets, which was massive during the first hour, in both cases. The dissolution profiles of all of the batches were comparable.

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por ® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference ME R , lecithin-containing ME L , and gelatin-containing ME G were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that ME L slowed down the drug release, while ME R and ME G have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME's application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in ME G and ME L had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel.

Objective: Transcutol ® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol ® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin., Methods: After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells., Results: Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7-39.8% from the microemulsion formulation and 90.6% from Transcutol ® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant ( p  < .05). Pearson correlation coefficients indicate a very high degree of dependence ( r  > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used., Conclusion: It can be stated that Transcutol ® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation.

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)