Preparation and Characterization of Indomethacin Supramolecular Systems with β-Cyclodextrin in Order to Estimate Photostability Improvement

Cyclodextrins have found wide application in contemporary chemistry, pharmacy and medicine. Because of their unique properties, cyclodextrins are constantly used in research on solubility or stability improvement, as well as other physicochemical properties of medicinal substances. Indomethacin (IND) is a photolabile molecule that also attracts the interest of researchers due to its therapeutic potential and the need to overcome its problematic photosensitivity. Supramolecular complexes of indomethacin with β-cyclodextrin (CD) are already known, and they show greater stability compared to complexes with other types of cyclodextrins. So far, however, the sensitivity to light of physical mixtures and inclusion complexes in the solid phase has not been studied, and their various stoichiometries have not yet been investigated. Due to this fact, the aim of the present study is to obtain supramolecular systems (inclusion complexes and physical mixtures) of indomethacin with three different amounts of β-cyclodextrin. Assessment of the photochemical stability of indomethacin-β-cyclodextrin systems in the solid state is performed in order to find the best correlation between IND stability and the amount of CD. Comparative analysis of physicochemical degradation for stoichiometry systems [CD:IND] = [1:1], [0.5:1] and [0.1:1] is performed by using ultraviolet spectroscopy, transmission—FTIR, reflection—ATR-FTIR infrared spectroscopy and DSC calorimetry.

Polymers Blending as Release Modulating Tool in Drug Delivery

Different polymeric materials have been used as drug delivery vehicles for decades. Natural, semisynthetic, and synthetic polymers each have their own specific characteristics and, due to the physicochemical limitations of each polymer, tuning the release rate and targeting the active ingredient to a specific organ or site of action is a complicated task for pharmaceutical scientists. In this regard, polymer blending has been considered as an attractive approach to fabricate novel and unique drug delivery systems with modified physical and/or chemical characteristics. There are three major polymer blending approaches that are used for drug delivery purposes: physical mixtures, core-shell model, and block copolymer model. Each of these types of polymer blends could significantly affect the loading capacities and the kinetics of drug release from the relevant formulations. Drug release from these blended polymers can be tuned through the changes in temperature and pH of the environment, and physiochemical properties of the target organs. Furthermore, the possible molecular interactions among polymers and drug molecules can significantly affect the drug release profile from these blended polymeric micro- and nanocarriers. In this review, first of all, different types of polymers and their various applications in biomedical sciences have been discussed and smart or stimuli responsive polymers are introduced and categorized based on their nature. Then, the purpose of polymer blending in drug delivery systems has been discussed. Different types of polymer blends including physical mixtures, core-shell polymeric carriers, and block copolymers have been summarized with focus on the effect of polymer blending on encapsulated drug release profiles. Finally, the consequence of each blending approach on drug release profile and kinetics of drug release have been mentioned in tabular format.

Miscibility and Solubility of Caffeine and Theophylline in Hydroxypropyl Methylcellulose

As amorphization may improve the solubility and bioavailability of a drug substance, the aim of this work was to assess to what extent the crystallinity of caffeine (CAF) and theophylline (TF) can be reduced by homogenization with a polymeric excipient. To realize this purpose, the physical mixtures of both methylxanthines with hydroxypropyl methylcellulose (HPMC) were examined using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier-transform infrared (FTIR) and Raman spectroscopy. Moreover, phase diagrams for the physical mixtures were calculated using theoretical data. Results of DSC experiments suggested that both CAF and TF underwent amorphization, which indicated proportional loss of crystallinity for methylxanthines in the mixtures with HPMC. Additionally, HSM revealed that no other crystalline or amorphous phases were created other than those observed for CAF and TF. FTIR and Raman spectra displayed all the bands characteristic for methylxanthines in mixtures with HPMC, thereby excluding changes in their chemical structures. However, changes to the intensity of the bands created by hydrogen bonds imply the formation of hydrogen bonding in the carbonyl group of methylxanthines and the methyl polymer group. This is consistent with data obtained using principal component analysis. The findings of these studies revealed the quantities of methylxanthines which may be dissolved in the polymer at a given temperature and the composition at which methylxanthines and polymer are sufficiently miscible to form a solid solution.

Enhancement of Solubility Ibuprofen by Solid Dispersion Technique on Natural Mucilage

In this study generally solid dispersions (SDs) of ibuprofen were prepared by for all intents and purposes melt dispersion technique using natural mucilage of Lemon seed as carrier, which really is quite significant. Physical mixtures (PMs) of ibuprofen literally were also prepared with the same carrier and in the same drug-carrier ratio (1:0.5, 1:1 and 1:1.5) to compare the dissolution profile, which generally is fairly significant. The solid dispersions and kind of physical mixtures for all intents and purposes were investigated for drug loading, saturation solubility and dissolution behavior in a subtle way. Saturation solubility study really actually was basically carried out in phosphate buffer (pH 7.4), 0.1 N HCL solution and distilled water, which kind of literally is quite significant. Solid dispersions for all intents and purposes particularly were mostly really found definitely fairly effective to literally kind of enhance the solubility of ibuprofen significantly in all the media, which actually is quite significant. Dissolution test specifically was mostly carried out in two different media, phosphate buffer (pH 7.4) and 0.1 N HCL. Solid dispersion containing Lemon seed mucilage at the ratio of 1:1.5 (drug: carrier) basically showed faster and sort of definitely higher drug release and basically was specifically really found to for the most part actually be most sort of effective among all the very actually solid dispersions in a generally big way, which kind of is fairly significant. Drug carrier interactions specifically specifically were studied by comparing Fourier definitely mostly Transform generally Infrared Spectroscopy (FT-IR) of particularly solid dispersions with pure drug which essentially revealed that the SDs specifically were kind of really stable in a pretty big way, which is fairly significant. So, fairly very solid dispersion may particularly be an definitely really effective technique to specifically enhance dissolution rate of ibuprofen, which kind of literally is fairly significant in a fairly big way.

Energetics of water in the Solar System

Water is vital for space exploration, from drinking to fuel reformation, and is naturally abundant in the Solar System [1–16]. While in-situ resource utilization (ISRU) requires vastly less energy than transporting resources, the energetics has scarcely been explored besides on Earth and limited analysis on Mars’ vapor. Here, we develop a thermodynamic framework to quantify the energy requirements for resource extraction from 18 water sources on 11 planetary bodies. We find that desalinating saline liquid brines, where available, could be the most energetically favorable option and the energy required to access water vapor can be four to ten times higher than accessing ice deposits. While desalination energetics are highly sensitive to salt concentration, we show that desalination energetics only vary by a factor of 2 with respect to the type of salt present. Additionally, unlike chemical mixtures, the minimum energetics are insensitive to composition in physical mixtures (e.g., ice-regolith and inert vapor mixtures). Additionally, by deriving and computing the equation-of-state for pure water, we extend the least work estimates of atmospheric water harvesting by 94°C lower than previous studies that depend on predetermined databases. The presented approach and data may inform decisions regarding water harvesting, habitation, and resource reformation.

Physicochemical compatibility studies of triclosan and flurbiprofen with excipients of pharmaceutical formulation using binary, ternary, and multi-combination approach

Background The aim of the study was to evaluate the suitability of triclosan (TCS) and flurbiprofen (FLB) with poly-ε-caprolactone (PCL), chitosan (CS), and Kolliphor® P188 (KP) for possible application in the design of nano-formulations. Results Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) revealed the physical characteristics of the various sample compositions without any apparent interaction. The Fourier transform infrared spectroscopy (FTIR)’s spectra of the physical mixtures showed their characteristic absorption bands with broadening and overlapping of bands in some instances, but no appearance of new bands was observed. Conclusion The study revealed the physical form stability of the evaluated components after the storage period and lack of definite pharmaceutical incompatibility between them. Thus, the selected drugs and excipients could be used for the development of pharmaceutical nano-formulations.

Dissolution profiles of fenbendazole from binary solid dispersions: a mathematical approach

Aim: Understanding a drug dissolution process from solid dispersions (SD) to develop formulations with predictable in vivo performance. Materials & methods: Dissolution data of fenbendazole released from the SDs and the control physical mixtures were analyzed using the Lumped mathematical model to estimate the parameters of pharmaceutical relevance. Results: The fit data obtained by Lumped model showed that all SDs have a unique dissolution profile with an error of ±4.1% and an initial release rate 500-times higher than the pure drug, without incidence of drug/polymer ratio or polymer type. Conclusion: The Lumped model helped to understand that the main factor influencing the fenbendazole release was the type formulation (SD or physical mixture), regardless of the type or amount of polymer used.

Synergistic application of continuous granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

This study demonstrated the first case of combining novel continuous granulation with powder-based pharmaceutical 3-dimensional (3D) printing processes to enhance the dissolution rate and physical properties of a poorly water-soluble drug. Powder bed fusion (PBF) and binder jetting 3D printing processes have gained much attention in pharmaceutical dosage form manufacturing in recent times. Although powder bed-based 3D printing platforms have been known to face printing and uniformity problems due to the inherent poor flow properties of the pharmaceutical physical mixtures (feedstock). Moreover, techniques such as binder jetting currently do not provide any solubility benefits to active pharmaceutical ingredients (APIs) with poor aqueous solubility (>40% of marketed drugs). For this study, a hot-melt extrusion-based versatile granulation process equipped with UV-Vis process analytical technology (PAT) tools for the in-line monitoring of critical quality attributes (i.e., solid-state) of indomethacin was developed. The collected granules with enhanced flow properties were mixed with vinylpyrrolidone-vinyl acetate copolymer and a conductive excipient for efficient sintering. These mixtures were further characterized for their bulk properties observing an excellent flow and later subjected to a PBF-3D printing process. The physical mixtures, processed granules, and printed tablets were characterized using conventional as well as advanced solid-state characterization. These characterizations revealed the amorphous nature of the drug in the processed granules and printed tablets. Further, the in vitro release testing of the tablets with produced granules as a reference standard depicted a notable solubility advantage (100% drug released in 5 minutes at >pH 6.8) over the pure drug and the physical mixture. Our developed system known as DosePlus combines innovative continuous granulation and PBF-3D printing process which can potentially improve the physical properties of the bulk drug and formulations in comparison to when used in isolation. This process can further find application in continuous manufacturing of granules and additive manufacturing of pharmaceuticals to produce dosage forms with excellent uniformity and solubility advantage.Abstract Figure