Sweeteners in Orodispersible Films: How Much is too Much?

Four natural sweeteners (sucrose, xylitol, fructose, and isomalt) were selected to examine the influence of their qualities and amounts on the characteristics of orodispersible films. Sodium carboxymethylcellulose (2% w/w) was utilized as the film-forming polymer and 1% w/w glycerol as a plasticizer. Films were produced through the solvent casting method, rendering them suitable for convenient application in community or hospital pharmacy settings. The physicochemical and optical properties of the films were analyzed, and Fourier-transform infrared analysis was carried out. All films exhibited acceptable disintegration time, uniformity of mass, thickness, and optical characteristics, with significant dependence (p<0.05) on both sweetener type and quantity. Disintegration time varied based on the employed method, as well as the characteristics and amount of sweetener. Additionally, all films maintained pH values within the oral cavity range, suggesting no potential irritancy upon administration. Fourier-transform infrared analysis confirmed the formation of the film and demonstrated compatibility between its components.

A Critical Assessment of Extemporaneous Formulations for Proton Pump Inhibitors: The Importance of Proper Vehicle Selection.

OBJECTIVE: To examine the influence of vehicles on the stability of extemporaneous suspensions of proton pump inhibitors (PPIs), to single out the formulation most suitable for children, providing appropriate evidence and arguments. METHODS: A review was performed of data identified from Medline, Embase, Science Direct, as well as public digital archive PubMed, including reference texts, related to the field of stability testing of extemporaneous PPI suspensions. RESULTS: Fourteen selected formulations of extemporaneous suspensions are presented and discussed. Depending on the vehicle and its composition, which was analyzed and explained in detail, the suspensions had various beyond-use dates (BUDs). CONCLUSIONS: Selected vehicles and the process of preparation had great influence on the stability of extemporaneous PPI suspensions. The suspension with the longest BUD has been singled out, which is especially suitable for use in newborns. Because an explanation is provided for the influence of individual vehicle components on the stability of the mentioned suspensions, this can aid not only in the selection of an adequate formulation, but also in the development of new ones, which will be suited to individual patients.

Inclusion complexes of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin with 2-hydroxypropyl-(-cyclodextrin: solubility and antimicrobial activity

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-ß-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-ß-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

3D Printing-A "Touch-Button" Approach to Manufacture Microneedles for Transdermal Drug Delivery.

Microneedles (MNs) represent the concept of attractive, minimally invasive puncture devices of micron-sized dimensions that penetrate the skin painlessly and thus facilitate the transdermal administration of a wide range of active substances. MNs have been manufactured by a variety of production technologies, from a range of materials, but most of these manufacturing methods are time-consuming and expensive for screening new designs and making any modifications. Additive manufacturing (AM) has become one of the most revolutionary tools in the pharmaceutical field, with its unique ability to manufacture personalized dosage forms and patient-specific medical devices such as MNs. This review aims to summarize various 3D printing technologies that can produce MNs from digital models in a single step, including a survey on their benefits and drawbacks. In addition, this paper highlights current research in the field of 3D printed MN-assisted transdermal drug delivery systems and analyzes parameters affecting the mechanical properties of 3D printed MNs. The current regulatory framework associated with 3D printed MNs as well as different methods for the analysis and evaluation of 3D printed MN properties are outlined.

In vitro pH dependent passive transport of ketoprofen and metformin.

The kinetics of passive transport of ketoprofen and metformin, as model substances for high and low permeability, respectively, across the artificial membrane under the influence of the pH of donor solution was investigated. There was an upward trend in the apparent permeation coefficient (P app) of ketoprofen with the decrease in pH to a value close to pKa. At the pH value below pKa the permeation coefficient had lower value, due to the higher retention of ketoprofen in the artificial membrane. Metformin is a low permeable compound, and the highest permeation values were recorded at pH 7.4. Two dissociation constants determine that metformin at physiological pH exists as a hydrophilic cationic molecule, i.e. predominantly in ionized form. At pH values below 2.8, metformin mainly exists in diprotonated form, and it was, thus, very poorly permeable. The highest retention, i.e. affinity of both ketoprofen and metformin to the membrane, was at the lowest pH values, which is explained by different mechanisms. At higher pH values of donor compartment the substances showed significantly less affinity to the membrane. The obtained values of apparent permeation coefficients at studied pH values showed good correlation with the obtained experimental values by other in vitro methods.

Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions.

Glaucoma is considered to be one of the biggest health problems in the world. It is the main cause of preventable blindness due to its asymptomatic nature in the early stages on the one hand and patients' non-adherence on the other. There are several approaches in glaucoma treatment, whereby this has to be individually designed for each patient. The first-line treatment is medication therapy. However, taking into account numerous disadvantages of conventional ophthalmic dosage forms, intensive work has been carried out on the development of novel drug delivery systems for glaucoma. This review aims to provide an overview of formulation solutions and strategies in the development of in situ gel systems, nanosystems, ocular inserts, contact lenses, collagen corneal shields, ocular implants, microneedles, and iontophoretic devices. The results of studies confirming the effectiveness of the aforementioned drug delivery systems were also briefly presented.

Microneedles: Characteristics, Materials, Production Methods and Commercial Development.

Although transdermal drug delivery systems (DDS) offer numerous benefits for patients, including the avoidance of both gastric irritation and first-pass metabolism effect, as well as improved patient compliance, only a limited number of active pharmaceutical ingredients (APIs) can be delivered accordingly. Microneedles (MNs) represent one of the most promising concepts for effective transdermal drug delivery that penetrate the protective skin barrier in a minimally invasive and painless manner. The first MNs were produced in the 90s, and since then, this field has been continually evolving. Therefore, different manufacturing methods, not only for MNs but also MN molds, are introduced, which allows for the cost-effective production of MNs for drug and vaccine delivery and even diagnostic/monitoring purposes. The focus of this review is to give a brief overview of MN characteristics, material composition, as well as the production and commercial development of MN-based systems.

Cytogenotoxicity of Inclusion Complexes of Diazepam with 2-Hydroxypropyl-ß-cyclodextrin.

Background Diazepam, as one of the most frequent prescribed drug from 1,4-benzodiazepine group, has certain limitations in pharmaceutical technology due to its poor solubility in water. By forming inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin, diazepam's biopharmaceutical properties can be greatly improved. Aim Aim of this research was to in vitro evaluate genotoxicity of prepared novel complexes of diazepam and their influence on proliferation of human peripheral blood lymphocytes. Methods For identification of possible genotoxicity of diazepam inclusion complexes, cytokinesis-block micronucleus assay has been chosen. Evaluated concentrations of two diazepam inclusion complexes were 0.2 µg/mL, 0.5 µg/mL and 1.0 µg/mL in cell culture. For a reference, in vitro cytogenotoxicity evaluation of diazepam alone has been conducted as well. Results Neither one of the diazepam, complexed nor non-complexed, in given concentrations showed genotoxicity, induced genetic damage or loss of genetic material. Conclusions Nuclear division index values, as indicators of cytostaticity and cytotoxicity suggested that investigated inclusion diazepam complexes induced accelerated proliferation of human peripheral blood lymphocytes in vitro, therefore possibly shortening the duration and dynamics of the cell cycle.

Stability of suspensions: theoretical and practical considerations before compounding.

Suspension stability can be theoretically estimated prior to the beginning of the formulating process based on the solid phase particle size, liquid phase density, and viscosity. Stokes equation can be used to predict suspension stability in order to save time and resources. The examples of these calculations for the assessment of suspension physical characteristics are given in this article. One parameter that cannot be theoretically estimated with precision is flocculation/deflocculation. Flocculation can be experimentally determined using the "jar test," and it is a critical parameter for the substances showing inclination toward caking. Suspensions will sediment in time; however, it is their key feature to be able to redisperse in order to preserve the efficacy and proper dosage. Bismuth subnitrate is practically insoluble in water, which makes it convenient for oral pharmaceutical suspensions, rather than the other pharmaceutical forms. Like the other bismuth compounds, it tends to cake in aqueous medium. In order to prevent formation of the solid sediment, controlled flocculation of the suspended bismuth subnitrate particles is recommended. The effect of the excipients (sodium citrate, Tween 20, propylene glycol, microcrystalline cellulose) on the transmittance of the prepared suspensions and the quantity and characteristics of the formed sediment were evaluated. Suspensions containing sodium citrate, as well as the formulations with sodium citrate and microcrystalline cellulose, based on their transmittance characteristics, were determined to be flocculating suspensions, regardless of the sodium citrate concentration used. The highest affinity towards formation of flocculating suspensions, with the highest transmittance value had microcrystalline cellulose with 15% (w/w) sodium citrate.

[Transdermal drug delivery systems]. / Transdermalni terapeutski sistemi.

Transdermal drug delivery systems are pharmaceutical preparations, intended to be applied to the unbroken skin in order to deliver the active ingredient(s) to the systemic circulation after passing through the skin barrier. Transdermal patches are formulated in different ways, but normally they consist of release liner, adhesive layer and backing layer. Active ingredient(s) can be incorporated in reservoir, matrix, adhesive, membrane-matrix and microreservoir. The releasing rate of active substances from patches is controlled by membrane, matrix and adhesive. Only several transdermal systems are available on the market today, because for the penetration of most substances skin represents a strong barrier. With transdermal systems it is possible to obtain a controllable and sustained plasma levels, to minimaze the risk of undesirable side effects and to avoid the hepatic first- pass metabolism. These devices are easy to apply and also to remove from the skin. Of a great pharmaceutical interest are also socalled cosmetic patches. They are applied with aim of cleaning and protecting the skin.