Orodispersible Dosage Forms with Rhinacanthin-Rich Extract as a Convenient Formulation Dedicated to Pediatric Patients.

Rhinacanthins, derived from Rhinacanthus nasutus, widely used in traditional medicine, exhibit antifungal, anticancer, antiviral, antibacterial, and antiplatelet aggregation effects. Recently, their anti-diabetic activity was confirmed, which makes them an interesting natural alternative in the therapy of the early stage of diabetes mellitus. The aim of this study was to demonstrate the possibility of formulating orodispersible tablets (ODTs) and orodispersible films (ODFs) containing rhinacanthin-rich extract (RRE). Tablets with 50 mg or 100 mg of RRE were produced by direct compression. ODFs were manufactured by casting of Lycoat RS 720 or polyvinyl alcohol solution with RRE and additional excipients. The mechanical properties and disintegration times of the prepared formulations were studied. The effectiveness of taste masking was analyzed with an electronic tongue system. Six months simplified stability studies were performed in conditions complying to ICH guidelines. Appropriate friability of ODTs was achieved, despite low tensile strength (0.45-0.62 MPa). All prepared ODFs successfully met the acceptance criteria regarding Young's modulus, tensile strength, and elongation at break. The observed variations in their mechanical properties were dependent on the type and quantity of polymers and plasticizers used. Disintegration time of ODTs ranged from 38.7 s to 54.2 s, while for ODFs from 24.2 to 40 s in the pharmacopoeial apparatus. Analyses made with the electronic tongue showed the significant taste-masking effect in both formulations. The addition of sucralose as a sweetener and menthol with mint flavor as a taste-masking agent was sufficient to mask an RRE's taste in the case of ODTs and ODFs. Stability studies of ODTs packed in the PVC/Alu blisters showed a decrease in the RRE content below 90% after 6 months. However, ODFs with PVA were physicochemically stable for 6 months while being stored in Alu/Alu sachets. Our study proved for the first time the possibility of the formulation of orodispersible dosage forms with RRE, characterized by good mechanical properties, disintegration time, and appropriate taste masking.

The Impact of the Preparation Method on the Properties of Orodispersible Films with Aripiprazole: Electrospinning vs. Casting and 3D Printing Methods.

Orodispersible films (ODFs) address the needs of pediatric and geriatric patients and people with swallowing difficulties due to fast disintegration in the mouth. Typically, they are obtained using the solvent casting method, but other techniques such as 3D printing and electrospinning have already been investigated. The decision on the manufacturing method is of crucial importance because it affects film properties. This study aimed to compare electrospun ODFs containing aripiprazole and polyvinyl alcohol with films prepared using casting and 3D printing methods. Characterization of films included DSC and XRD analysis, microscopic analysis, the assessment of mechanical parameters, disintegration, and dissolution tests. Simplified stability studies were performed after one month of storage. All prepared films met acceptance criteria for mechanical properties. Electrospun ODFs disintegrated in 1.0 s, which was much less than in the case of other films. Stability studies have shown the sensitivity of electrospun films to the storage condition resulting in partial recrystallization of ARP. These changes negatively affected the dissolution rate, but mechanical properties and disintegration time remained at a desirable level. The results demonstrated that electrospun fibers are promising solutions that can be used in the future for the treatment of patients with swallowing problems.

Orodispersible films containing ball milled aripiprazole-poloxamer®407 solid dispersions.

This research aimed at developing ODFs containing an antipsychotic drug - aripiprazole (ARP). ARP, as a BCS II class molecule, requires enhancing its water solubility prior to formulating. Therefore, a solid dispersion of ARP - Poloxamer® 407 was prepared by ball milling, then incorporated into the films. It was found that co-processing led to an over 100-fold increase in drug solubility in comparison with pure drug. Moreover, ODFs with solid dispersion showed faster drug release (>95% below 15 min) and disintegration (<30 s), compared with raw ARP films. These results are believed to be due to the solubilization effect of poloxamer and enhanced wettability of the film. Films containing solid dispersions were found to possess smoother film surfaces and favorable mechanical properties - flexibility and strength. The ODF formulations, prepared by a casting method, were based on three different polymers (Kollicoat® IR, Kollicoat® Protect or PVA). It was found that not only the form of the incorporated drug, but also the type of film-forming polymer had an impact on the analyzed parameters. The use of PVA was beneficial in the film formulation with aripiprazole in comparison to other tested film-forming polymers.

The impact of polymers on 3D microstructure and controlled release of sildenafil citrate from hydrophilic matrices.

Sildenafil citrate has short biological half-life in humans. Thus, matrix tablets of controlled release were designed and prepared by compaction on the basis of hydrophilic polymers, i.e. HPMC, sodium alginate, carbomer, poloxamer and their mixtures. The impact of these polymers on sildenafil release in vitro and its pharmacokinetics in vivo was evaluated. Since drug release rate from hydrophilic matrices can be govern by the porosity of the matrix, the microstructure of tablets was studied using X-ray microcomputed tomography. 3D network of either open (percolating) or closed (non-percolating) pores was reconstructed. The tortuosity and the diameter of both kinds of pores were determined. Their spatial distribution within the matrix was analyzed in linear and radial direction. Polymer-dependent characteristics of the open pores (Ø > 2 µm) architecture was shown. The release profiles of sildenafil from matrix tablets fitted to Korsmeyer-Peppas model (r2: 0.9331-0.9993) with either Fickian diffusion or anomalous transport involved. Mean dissolution time (MDT) from tablets made of HPMC, carbomer or a mixture of HPMC and sodium alginate (2:1) was ca. 100 min, which was more than twelve times longer as compared to matrices prepared of silicified microcrystalline cellulose (MDT = 8 min). MDT correlated with the number of the open pores (Pearson's r = 0.94). Sustained release of sildenafil from ground carbomer tablets reflected in the slow absorption of the drug (tmax = 5.0 ±â€¯1.2 h) in vivo and the relative bioavailability of 151%. Interestingly, the relative bioavailability of sildenafil from binary matrices composed of HPMC and sodium alginate (2:1) was almost four times higher than that of sildenafil alone.

3D printed orodispersible films with Aripiprazole.

Three dimensional printing technology is gaining in importance because of its increasing availability and wide applications. One of the three dimensional printing techniques is Fused Deposition Modelling (FDM) which works on the basis of hot melt extrusion-well known in the pharmaceutical technology. Combination of fused deposition modelling with preparation of the orodispersible film with poorly water soluble substance such as aripiprazole seems to be extra advantageous in terms of dissolution rate. 3D printed as well as casted films were compared in terms of physicochemical and mechanical properties. Moreover, drug-free films were prepared to evaluate the impact of the extrusion process and aripiprazole presence on the film properties. X-ray diffractometry and thermal analyses confirmed transition of aripiprazole into amorphous state during film preparation using 3D printing technique. Amorphization of the aripiprazole and porous structure of printed film led to increased dissolution rate in comparison to casted films, which, however have slightly better mechanical properties due to their continuous structure. It can be concluded that fused deposition modelling is suitable technique and polyvinyl alcohol is applicable polymer for orodispersible films preparation.

PRINTING TECHNIQUES: RECENT DEVELOPMENTS IN PHARMACEUTICAL TECHNOLOGY.

In the last few years there has been a huge progress in a development of printing techniques and their application in pharmaceutical sciences and particularly in the pharmaceutical technology. The variety of printing methods makes it necessary to systemize them, explain the principles of operation, and specify the possibilities of their use in pharmaceutical technology. This paper aims to review the printing techniques used in a drug development process. The growing interest in 2D and 3D printing methods results in continuously increasing number of scientific papers. Introduction of the first printed drug Spritam@ to the market seems to be a milestone of the 3D printing development. Thus, a particular aim of this review is to show the latest achievements of the researchers in the field of the printing medicines.