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.

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The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The interactions of drug-cyclodextrin in solution were investigated by the phase-solubility analysis. Diazepam (nitrazepam) content in aqueous complexation medium was analyzed UV spectrophotometrically. Classical solubility data were used to derive apparent stability constants (K 1:1 ) which were used to derive thermodynamic parameters for the diazepam (nitrazepam)-cyclodextrin complexes. Since all phase solubility plots were of A L-types, and calculated Slopes after linear regression analysis were found to be less than 1, it could be assumed that stoichiometry of the formed binary systems was , respectively. Formation of inclusion complexes substantially increases the water solubility of diazepam and nitrazepam. Diazepam and nitrazepam dissolution thermodynamics in aqueous 2-HP-β-CD were characterized by spontaneous and endothermic dissolution and hydrophobic interactions.

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.

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When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1 , while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2 , the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8.

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.