3D Printed Buccal Films for Prolonged-Release of Propranolol Hydrochloride: Development, Characterization and Bioavailability Prediction

Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties and drug release profiles of gelatin-based films. The Fourier-transform infrared spectroscopy showed that hydrogen bonding between gelatin and PVP formed during printing. In the other blend, neither the esterification of PVA nor gelatin occurred. Differential scanning calorimetry revealed the presence of partial helical structures. In line with these results, the mechanical properties and drug release profiles were different for each blend. Formulation with gelatin-PVP and PRH showed higher tensile strength, hardness, and adhesive strength but slower drug release than formulation with gelatin-PVA and PRH. The in silico population simulations indicated increased drug bioavailability and decreased inter-individual variations in the resulting pharmacokinetic profiles compared to immediate-release tablets. Moreover, the simulation results suggested that reduced PRH daily dosing can be achieved with prolonged-release buccal films, which improves patient compliance.

Electrospun Structural Hybrids of Acyclovir-Polyacrylonitrile at Acyclovir for Modifying Drug Release

In traditional pharmaceutics, drug–crystalline nanoparticles and drug–polymer composites are frequently explored for their ability to modify drug release profiles. In this study, a novel sort of hybrid with a coating of acyclovir crystalline nanoparticles on acyclovir-polyacrylonitrile composites was fabricated using modified, coaxial electrospinning processes. The developed acyclovir-polyacrylonitrile at the acyclovir nanohybrids was loaded with various amounts of acyclovir, which could be realized simply by adjusting the sheath fluid flow rates. Compared with the electrospun composite nanofibers from a single-fluid blending process, the nanohybrids showed advantages of modifying the acyclovir release profiles in the following aspects: (1) the initial release amount was more accurately and intentionally controlled; (2) the later sustained release was nearer to a zero-order kinetic process; and (3) the release amounts at different stages could be easily allocated by the sheath fluid flow rate. X-ray diffraction results verified that the acyclovir nanoparticles were in a crystalline state, and Fourier-transform infrared spectra verified that the drug acyclovir and the polymer polyacrylonitrile had a good compatibility. The protocols reported here could pave the way for developing new types of functional nanostructures.

Development and Characterization of pH-Dependent Cellulose Acetate Phthalate Nanofibers by Electrospinning Technique

The aim of this work was to obtain pH-dependent nanofibers with an electrospinning technique as a novel controlled release system for the treatment of periodontal disease (PD). Cellulose acetate phthalate (CAP) was selected as a pH-sensitive and antimicrobial polymer. The NF was optimized according to polymeric dispersion variables, polymer, and drug concentration, and characterized considering morphology, diameter, entrapment efficiency (EE), process efficiency (PE), thermal properties, and release profiles. Two solvent mixtures were tested, and CHX-CAP-NF prepared with acetone/ethanol at 12% w/v of the polymer showed a diameter size of 934 nm, a uniform morphology with 42% of EE, and 55% of PE. Meanwhile, CHX-CAP-NF prepared with acetone/methanol at 11% w/v of polymer had a diameter of 257 nm, discontinuous nanofiber morphology with 32% of EE, and 40% of PE. EE and PE were dependent on the polymer concentration and the drug used in the formulation. Studies of differential scanning calorimetry (DSC) showed that the drug was dispersed in the NF matrix. The release profiles of CHX from CHX-CAP-NF followed Fickian diffusion dependent on time (t0.43−0.45), suggesting a diffusion–erosion process and a matrix behavior. The NF developed could be employed as a novel drug delivery system in PD.

Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery

The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

Reactive Structures of Ammonia MILD Combustion in Diffusion Ignition Processes

Reactive structures have been analyzed, when ammonia is used as a fuel, in a steady 1D counterflow diffusion flame layer, mimicking diffusion ignition processes. The characterization has been carried out in a wide range of feeding parameters under Moderate or Intense Low-oxygen Dilution (MILD) combustion conditions. Both the Hot-Fuel-Diluted-Fuel (HFDF) and Hot-Oxidant-Diluted-Fuel (HODF) configurations were studied to analyze the main effects of the inlet feeding conditions on the oxidative structures. The reaction zone has been analyzed in terms of temperature and heat release profiles in the mixture fraction space for various ranges of inlet parameters, using a standard code and a validated chemical kinetic scheme. Several features of the reaction zone have been recognized as reported also in previous works for hydrocarbon flames. They were used as discriminative for the achievement of various combustion regimes. In particular, the flame thickening process and the absence of correlation between the maximum heat release and the stoichiometric mixture fraction were analyzed to build maps of behaviors. The latter were reported on an inlet preheating level-temperature increase plane for fixed values of the bulk strain rate and system pressures. Another relevant feature previously reported with hydrocarbons in the literature, in Hot Diluted Diffusion Ignition (HDDI) processes under MILD conditions, was the pyrolysis depression. The latter characteristic has been not observed when ammonia is used as a fuel, for the operative conditions here investigated. Indeed, the heat release profiles do not show the presence of negative heat release regions. The results obtained for the HFDF configuration are strongly dependent on the system pressure level. Finally, the HODF condition has been also analyzed for ammonia at the atmospheric pressure. Boundaries of the combustion regimes and reactive structure features showed several differences between HFDF and HODF cases with respect to the inlet parameters.

Hydrophilic Excipient-Independent Drug Release from SLA-Printed Pellets

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.

The Effect of Particle Size on the Physical Characteristics and Drug-release Behavior of Mini-tablets

This study aimed to investigate the influence of particle size of the excipients on the behavior of mini-tablets in terms of physical characteristics and drug release profiles. Material and methods: All of the mini-tablets based on HPMC, PEG 6K and PEO 8M PVP produced high quality mini-tablets from both sieve fractions while 90F was very fragile. Results: Crushing strength values were the most pronounced difference between the mini-tablets from all formulations. The PEO 8M-based mini-tablets showed the highest values and deformation behavior instead of fracture. Water absorption and drug release profiles also showed intriguing and different results between the various formulations. Conclusion: The results suggested that even though different particle size has limited effect on the physical characteristic of the product, it may have a significant effect on its drug dissolution profile. HIGHLIGHTS The particle size of powders or granules can influence the physical properties and release profiles of tablets, particularly mini-tablets PEG 6K and PEO 8M mini-tablets from the larger sieve fraction variation absorbed less moisture and released drugs faster than their counterparts, whereas HPMC and PVP 90F mini-tablets from both sieve fractions exhibited a similar pattern in terms of moisture uptake and drug release profiles PEO 8M mini-tablets of both sieve fractions displayed almost linear release profiles with the highest crushing strength than the rest of the formulations GRAPHICAL ABSTRACT

The Effects of Accelerated Temperature-Controlled Stability Systems on the Release Profile of Primary Bile Acid-Based Delivery Microcapsules

Introduction: Bile acid-based drug encapsulation for oral delivery has been recently explored in our laboratory and has shown to be beneficial in terms of drug-targeted delivery and release profile, but stability at various temperatures has not previously been examined; hence, this is the aim of this study. Methods: Various types of bile acid-based microcapsules containing the drug metformin were produced and tested for accelerated temperature-controlled profiles, as well as morphology, elemental composition, drug content, resilience, floatability, wettability and release profiles at various pH values. Results: Accelerated temperature-controlled analysis showed negligible effects on morphology, size, or shape at very low temperatures (below 0 °C), while higher temperatures (above 25 °C) caused alterations. Drug contents, morphology and elemental composition remained similar, while wettability and the release profiles showed formulation-dependent effects. Discussion and Conclusion: Results suggest that bile acid-based microcapsules containing metformin are affected by temperature; hence, their shelf life is likely to be affected by storage temperature, all of which have a direct impact on drug release and stability profiles.

pH-responsive polymer-based biomacromolecule nanosponges as biodegradable carriers for DOX delivery

Cellulose is the most abundant renewable biomaterial on earth and beta-cyclodextrin (BCD) is among the most commonly used biocompatible drug encapsulation agents. Combining these bio-organic materials is a very powerful approach to greatly enhance the bioavailability of many drugs. These systems also allow for optimal selective drug release profiles, high biocompatibility, as well as “green nanomedicine” approaches that are eco-friendly in their synthesis and have minimal ecological toxicity. herein, we designed a new type of green and biopolymer-based nanosponge drug carriers which is polymerized by crosslinking beta-cyclodextrin ethylene diamine (βCD-EDA) with bifunctional hairy nanocellulose (BHNC). BHNC contains, besides aldehyde groups, carboxyl groups which can react with amino groups in βCD-EDA. Firstly, the crosslinker βCD-EDA was obtained through a simple nucleophilic substitution reaction between beta-cyclodextrin carbonyl imidazole (βCD-CI) and ethylene diamine (EDA). Secondly, BHNC was functionalized with the crosslinker βCD-EDA through a facile nucleophilic substitution crosslinking reaction of the BHNC activated carboxyl groups by the amines of βCD-EDA. We refer to the polymerized highly crosslinked BHNC-βCD-EDA network as BBE. Various ratios of βCD-EDA and BHNC were polymerized with the help of DMTMM as an activator, which resulted in different morphological shapes of BBE, and thus in different release profiles and pH-responsiveness. Unlike other polymer-based βCDs and nanosponges, these new types of crosslinked polymer were prepared in a green and safe solvent (water) and with very short reaction times and at low temperatures. Finally, the BBE polymers were tested as biocompatible nanocarriers for controllable doxorubicin (DOX) delivery. These hyper crosslinked polymers show a high capacity for loading DOX with extended drug release. Furthermore, breast cancer cell cultures show lower cell viability when DOX was loaded in various BBEs than control samples or DOX alone, indicating that our DOX-BBE drug delivery systems are better anticancer agents than DOX alone.