The Impact of Liquid Components on Alteration of the Adhesion of Polyacrylate and Silicone Patches.

Polyacrylates and polysiloxanes are polymers used in pressure-sensitive adhesive (PSA) patches. Liquid additives are co-solvents of the active substances or permeation enhancers, and their compatibility with the polymeric matrix and the effect on adhesive properties should be considered. The patches were prepared from commercial polyacrylates (three types of Duro-Tak®) and siloxanes (Bio-PSA® and Soft Skin Adhesive®). Propylene glycol, polyoxyethylene glycol, isopropyl myristate, triacetin, triethyl citrate and silicone oil were added (10% w/w). Formulations were evaluated microscopically and with a texture analyzer in terms of in vitro adhesiveness and hardness. Only silicone oil was compatible with the silicone matrices. The best compatibility of acrylic PSA was observed with triethyl citrate; one out of three Duro-Tak matrices was incompatible with every additive. In all compositions, the adhesiveness was impaired by the liquid additives. A significant drop in adhesiveness was noted after immersion of the patches in buffer and drying. The probe tack test was considered as the most useful for evaluation of the effect of the liquid additive on adhesiveness, but the results obtained with a spherical and cylindrical probe were contradictory. The structural changes caused by the additives were also demonstrated by a 90° peel test, considered as complementary to the tack test.

Development of a 3D-Printable, Porous, and Chemically Active Material Filled with Silica Particles and its Application to the Fabrication of a Microextraction Device.

We report on the first successful attempt to produce a silica/polymer composite with retained C18 silica sorptive properties that can be reliably printed using three-dimensional (3D) FDM printing. A 3D printer provides an exceptional tool for producing complex objects in an easy and inexpensive manner and satisfying the current custom demand of research. Fused deposition modeling (FDM) is the most popular 3D-printing technique based on the extrusion of a thermoplastic material. The lack of appropriate materials limits the development of advanced applications involving directly 3D-printed devices with intrinsic chemical activity. Progress in sample preparation, especially for complex sample matrices and when mass spectrometry is favorable, remains a vital research field. Silica particles, for example, which are commonly used for extraction, cannot be directly extruded and are not readily workable in a powder form. The availability of composite materials containing a thermoplastic polymer matrix and dispersed silica particles would accelerate research in this area. This paper describes how to prepare a polypropylene (PP)/acrylonitrile-butadiene-styrene (ABS)/C18-functionalized silica composite that can be processed by FDM 3D printing. We present a method for producing the filament as well as a procedure to remove ABS by acetone rinsing (to activate the material). The result is an activated 3D-printed object with a porous structure that allows access to silica particles while maintaining macroscopic size and shape. The 3D-printed device is intended for use in a solid-phase microextraction (SPME) procedure. The proposed composite's effectiveness is demonstrated for the microextraction of glimepiride, imipramine, and carbamazepine. The complex honeycomb geometry of the sorbent has shown to be superior to the simple tubular sorbent, which proves the benefits of 3D printing. The 3D-printed sorbent's shape and microextraction parameters were fine-tuned to provide satisfactory recoveries (33-47%) and high precision (2-6%), especially for carbamazepine microextraction.

The Use of Calcium Phosphate-Based Starter Pellets for the Preparation of Sprinkle IR MUPS Formulation of Rosuvastatin Calcium.

Sprinkle formulations represent an interesting concept of medicinal products aimed at the steadily growing population of patients suffering from swallowing difficulties (dysphagia). In the present work, immediate-release sprinkle MUPS (multiple-unit pellet system) containing rosuvastatin calcium as a model drug substance was successfully developed. The formulation was prepared by drug layering technique using novel calcium phosphate-based starting pellets (PharSQ® Spheres CM) of three different particle sizes. The study showed that the developed multiparticulates were characterized by uniform distribution of coating layers thickness, as well as fast dissolution rate (more than 85% of rosuvastatin calcium dissolved within 30 min, as required by the relevant USP/NF monograph). Rosuvastatin calcium, like other statins, has a bitter, unpleasant taste. Investigations conducted with an electronic tongue suggested that the developed formulation achieved the desired taste-masking efficiency. The effect was found to be particle size-dependent, improving as the size of the multiparticulates increased.

Microscopic and Spectroscopic Imaging and Thermal Analysis of Acrylates, Silicones and Active Pharmaceutical Ingredients in Adhesive Transdermal Patches.

Dermal or transdermal patches are increasingly becoming a noteworthy alternative as carriers for active pharmaceutical ingredients (APIs), which makes their detailed physicochemical evaluation essential for pharmaceutical development. This paper demonstrates mid-infrared (FTIR) and Raman spectroscopy with complementary microscopic methods (SEM, optical and confocal Raman microscopy) and differential scanning calorimetry (DSC) as tools for the identification of the state of model API (testosterone TST, cytisine CYT or indomethacin IND) in selected adhesive matrices. Among the employed spectroscopic techniques, FTIR and Raman may be used not only as standard methods for API identification in the matrix, but also as a means of distinguishing commercially available polymeric materials of a similar chemical structures. A novel approach for the preparation of adhesive polymers for the FTIR analysis was introduced. In silicone matrices, all three APIs were suspended, whereas in the case of the acrylic PSA, Raman microscopy confirmed that only IND was dissolved in all three acrylic matrices, and the dissolved fraction of the CYT differed depending on the matrix type. Moreover, the recrystallization of TST was observed in one of the acrylates. Interestingly, a DSC analysis of the acrylic patches did not confirm the presence of the API even if the microscopic images showed suspended particles.

Directly compressible formulation of immediate release rosuvastatin calcium tablets stabilized with tribasic calcium phosphate.

Reliable and stable tablet formulations for rosuvastatin calcium (RSC) in four strengths: 5 mg, 10 mg, 20 mg, and 40 mg have been developed. Rosuvastatin is a cholesterol-lowering statin drug and is known to be unstable during storage. The possibility of its stabilization with inorganic salts of multivalent metals has already been reported in the literature. In the present study, a special grade of tribasic calcium phosphate excipient was used to chemically stabilize RSC in a directly compressible immediate release tablet formulation. The developed tablets exhibited good mechanical properties (breaking force ranging from 177 N to 250 N depending on tablet strength), rapid disintegration (less than three minutes) and fast dissolution rate (85% of the drug substance dissolved within 15 minutes) as well as satisfactory chemical stability during storage under stress conditions (50 °C/80% RH), even compared to the reference commercial product.

Potential of mucoadhesive chitosan glutamate microparticles as microbicide carriers - antiherpes activity and penetration behavior across the human vaginal epithelium.

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of in vitro antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. Ex vivo penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.

Spectroscopic evaluation on pseudopolymorphs of sodium naproxen.

This paper demonstrates the assessment of vibrational spectroscopy methods such as middle infrared, near infrared and Raman spectroscopy (FTIR, FT-NIR, Raman) for the identification of pseudopolymorphic forms of a model active pharmaceutical ingredient (API) - sodium naproxen (NpxNa). NpxNa, in the form of three different pseudopolymorphs, was investigated by methods dedicated for solid state characterization: DSC (differential scanning calorimetry), XPRD (powder X-ray diffraction), SEM (scanning electron microscopy) and Karl Fischer titration. Novelty in the results sourced in the usage of the method not applied so far to identify pseudopolymorphic forms of NpxNa, that is, FTIR and FT-NIR. Based on the obtained reproduceable results, various pseudopolymorphic forms were successfully evaluated. Spectroscopic data were correlated with DSC and XPRD results. It was concluded that the combination of band's variations visible on the spectra of pseudopolymorphic forms will allow to interpretate the results unequivocally in case of crucial stability tests of medicinal substance or during on-line pharmaceutical process development by FTIR, FT-NIR and Raman spectroscopy.

Controlled Drug Release by the Pore Structure in Polydimethylsiloxane Transdermal Patches.

The use of polydimethylsiloxanes (PDMS) as a drug carrier in transdermal adhesive patches is limited and there is insufficient data on the polymer structure and diffusivity, especially when additives modify the matrix. PDMS films with liquid additives (10% w/w): silicone oil (SO), polyoxyethylene glycol (PEG) or propylene glycol (PG) were prepared and indomethacin (IND; 5% w/w) was incorporated as a model active substance. The microstructure of the PDMS matrix and its permeability to water was investigated and correlated to the kinetics of the in-vitro IND release from the film. Three microscopic techniques were used to characterize in detail the microstructure of PDMS films: scanning electron microscopy, fluorescent microscopy and atomic force microscopy. PDMS films with hydrophilic PEG or PG showed different two-phase structures. A two-fold increase in steady-state flux of IND and increased water transport in the presence of PEG was attributed to the pore-like channels created by this polar solvent in the PDMS matrix. This effect was not observed in the films with PG, where only discontinuous droplet-like structures were visible. All additives significantly changed the tensile parameters of the films but the effects were not very pronounced.

Physical and Mechanical Evaluation of Silicone-Based Double-Layer Adhesive Patch Intended for Keloids and Scar Treatment Therapy.

Growing interest in silicone elastomers for pharmaceutical purposes is due to both their beneficial material effect for scar treatment and their potential as drug carriers. Regarding their morphological structure, silicone polymers possess unique properties, which enable a wide range of applicability possibilities. The present study focused on developing a double-layer adhesive silicone film (DLASil) by evaluating its physical and mechanical properties, morphology, and stability. DLASil suitability for treatment of scars and keloids was evaluated by measurement of tensile strength, elasticity modulus, and elongation. The results indicated that mechanical and physical properties of the developed product were satisfying.

Double layer adhesive silicone dressing as a potential dermal drug delivery film in scar treatment.

The present studies focused on the evaluation of design of an adhesive silicone film intended for scar treatment. Developed silicone double layer film was examined in terms of its future relevance to therapy and applicability on the human skin considering properties which included in vitro permeability of water vapor and oxygen. In order to adapt the patches for medical use in the future there were tested such properties as in vitro adhesion and occlusion related to in vivo hydration. From the silicone rubbers double layer silicone film was prepared: a non-adhesive elastomer as a drug carrier (the matrix for active substances - enoxaparin sodium - low molecular weight heparin) and an adhesive elastomer, applied on the surface of the matrix. The novel adhesive silicone film was found to possess optimal properties in comparison to commercially available silicone dressing: adhesion in vivo, adhesion in vitro - 11.79N, occlusion F=85% and water vapor permeability in vitro - WVP=105g/m(2)/24h, hydration of stratum corneum in vivoH=61-89 (RSD=1.6-0.9%), oxygen permeation in vitro - 119-391 cm(3)/m(2)/24 (RSD=0.17%). In vitro release studies indicated sufficient LMWH release rate from silicone matrix. Developed novel adhesive silicone films were considered an effective treatment of scars and keloids and a potential drug carrier able to improve the effectiveness of therapy.