Characteristics of soy films as affected by transglutaminase cross-linking and inclusions of pectin and protein enhancers.

Previously, we showed that water extract (soymilk, except pH was increased to 8 from 6.5) of whole soybean could be used directly as a raw material for producing edible soy films by deposition of the film-forming solution (soy extract with enhancers). However, the strength of such soy films needed improvement because they were weak. The purpose of this study was to investigate how transglutaminase (TG) cross-linking reactions and film enhancers, including pectin (low- and high-methoxyl pectin), whey protein isolate (WPI), and soy protein isolate (SPI), improve the physical properties of soy films. Soy films prepared with TG had tensile strength (TS) of 3.01 MPa and puncture strength (PS) of 0.78 MPa, which were higher by as much as 51% and 30% than that of soy films without TG treatment, respectively. Pectin showed significant effects on the mechanical properties of TG-added soy films in terms of TS, PS, and % elongation. On the other hand, only TS and PS were increased by the addition of WPI or SPI. Heat curing had a significant effect on soy film's physical properties. TG treatment significantly reduced film solubility when soaked in water and various levels of acid (vinegar) and base (baking soda) solutions. Under the experimental conditions of 35 unit TG and 28 min of reaction, the degrees of cross-linking were evidenced by the disappearance of individual protein subunits, except the basic subunit of glycinin, and the reduction of 21% of lysine residues of the proteins. HIGHLIGHTS: Edible soy films were made with transglutaminase and about 21% lysine cross-linked. The mechanical strength of soy films was increased by incorporating film enhancers. Transglutaminase enhanced the mechanical properties of soy films.

Investigating extrusion impact on functional, textural properties, morphological structure, and molecular interactions in hulless barley-based extruded snacks supplemented with mung bean.

The effect of varying extrusion conditions on the functional properties of hulless barley-mung bean (70:30) extruded snacks was investigated using response surface methodology with feed moisture (FM), barrel temperature (BT), and screw speed (SS) as process variables. Results revealed significant impacts on functional characteristics with varying extrusion conditions. Bulk density (BD) of extruded snacks ranged from 0.24 to 0.42 g/cm3, showing that lower FM and higher BT results in lower BD while it increased with increasing FM, SS, and BT. The expansion ratio (ER) of extruded snacks ranged between 2.03 and 2.33, showing BT and SS had a desirable positive effect, whereas increasing FM led to decreased ER. Increasing BT and SS depicted a negative effect on water absorption index, whereas FM showed positive effect, which ranged between 4.21 and 4.82 g/g. A positive effect on water solubility index was depicted by BT and SS, which ranges between 9.01% and 13.45%, as higher SS and BT led to starch degradation and increased solubility suggesting better digestibility. The hardness of extruded snacks ranged from 32.56 to 66.88 Newton (N), showing increasing FM increased hardness, whereas higher SS and BT resulted in lowering the hardness. Scanning electronic microscope (SEM) analysis revealed structural changes in extrudates in comparison with nonextruded flour, indicating starch gelatinization and pore formation affected by varying processing parameters. Shifts in absorption bands were observed in Fourier transform infrared spectroscopy (FT-IR), suggesting structural changes in starch and protein. Understanding the effects of extrusion parameters on product properties can help tailored production to meet consumers' preferences and the development of functional snacks with improved nutritional quality.

Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations.

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.

Streamlining heterologous expression of top carbonic anhydrases in Escherichia coli: bioinformatic and experimental approaches.

BACKGROUND: Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO2 to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO2 capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications. RESULTS: In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity. CONCLUSIONS: Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli.

In vitro and in vivo dissolution of biocompatible S59 glass scaffolds.

Fabrication of porous tissue-engineering scaffolds from bioactive glasses (BAG) is complicated by the tendency of BAG compositions to crystallize in thermal treatments during scaffold manufacture. Here, experimental biocompatible glass S59 (SiO2 59.7 wt%, Na2O 25.5 wt%, CaO 11.0 wt%, P2O5 2.5 wt%, B2O3 1.3 wt%), known to be resistant to crystallization, was used in sintering of glass granules (300-500 µm) into porous scaffolds. The dissolution behavior of the scaffolds was then studied in vivo in rabbit femurs and under continuous flow conditions in vitro (14 days in vitro/56 days in vivo). The scaffolds were osteoconductive in vivo, as bone could grow into the scaffold structure. Still, the scaffolds could not induce sufficiently rapid bone ingrowth to replace the strength lost due to dissolution. The scaffolds lost their structure and strength as the scaffold necks dissolved. In vitro, S59 dissolved congruently throughout the 14-day experiments, resulting in only a slight reaction layer formation. Manufacturing BAG scaffolds from S59 that retain their amorphous structure was thus possible. The relatively rapid and stable dissolution of the scaffold implies that the glass S59 may have the potential to be used in composite implants providing initial strength and stable, predictable release of ions over longer exposure times.

Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations.

Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.

Nanosuspension-Based Repaglinide Fast-Dissolving Buccal Film for Dissolution Enhancement.

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.

Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53.

Purpose: Over the last few years, covalent fragment-based drug discovery has gained significant importance. Thus, striving for more warhead diversity, we conceived a library consisting of 20 covalently reacting compounds. Our covalent fragment library (CovLib) contains four different warhead classes, including five α-cyanoacacrylamides/acrylates (CA), three epoxides (EO), four vinyl sulfones (VS), and eight electron-deficient heteroarenes with a leaving group (SNAr/SN). Methods: After predicting the theoretical solubility of the fragments by LogP and LogS during the selection process, we determined their experimental solubility using a turbidimetric solubility assay. The reactivities of the different compounds were measured in a high-throughput 5,5'-dithiobis-(2-nitrobenzoic acid) DTNB assay, followed by a (glutathione) GSH stability assay. We employed the CovLib in a (differential scanning fluorimetry) DSF-based screening against different targets: c-Jun N-terminal kinase 3 (JNK3), ubiquitin-specific protease 7 (USP7), and the tumor suppressor p53. Finally, the covalent binding was confirmed by intact protein mass spectrometry (MS). Results: In general, the purchased fragments turned out to be sufficiently soluble. Additionally, they covered a broad spectrum of reactivity. All investigated α-cyanoacrylamides/acrylates and all structurally confirmed epoxides turned out to be less reactive compounds, possibly due to steric hindrance and reversibility (for α-cyanoacrylamides/acrylates). The SNAr and vinyl sulfone fragments are either highly reactive or stable. DSF measurements with the different targets JNK3, USP7, and p53 identified reactive fragment hits causing a shift in the melting temperatures of the proteins. MS confirmed the covalent binding mode of all these fragments to USP7 and p53, while additionally identifying the SNAr-type electrophile SN002 as a mildly reactive covalent hit for p53. Conclusion: The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1 °C and -9.1 °C.

Heterogenous Expression and Purification of Lipid II Flippase from Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a common pathogen with strains that are resistant to existing antibiotics. MurJ from S. aureus (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target. OBJECTIVE: In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment. METHODS: SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied. RESULTS: SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ. CONCLUSION: The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.

Characterization of Peptide Antibodies by Epitope Mapping Using Resin-Bound and Soluble Peptides.

Characterization of peptide antibodies through identification of their target epitopes is of utmost importance, as information about epitopes provide important knowledge, among others, for discovery and development of new therapeutics, vaccines, and diagnostics.This chapter describes a strategy for mapping of continuous peptide antibody epitopes using resin-bound and soluble peptides. The approach combines three different types of peptide sets for full characterization of peptide antibodies; (i) overlapping peptides, used to locate antigenic regions; (ii) truncated peptides, used to identify the minimal peptide length required for antibody binding; and (iii) substituted peptides, used to identify the key residues important for antibody binding and to determine the specific contribution of key residues. For initial screening, resin-bound peptides are used for epitope estimation, while soluble peptides subsequently are used for final epitope characterization and identification of critical hot spot residues. The combination of resin-bound peptides and soluble peptides for epitope mapping provides a time-saving and straightforward approach for characterization of antibodies recognizing continuous epitopes, which applies to peptide antibodies and occasionally antibodies directed to larger proteins as well.

Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling.

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development.

Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

1,3,5-Triaza-7-phosphaadamantane and Cyclohexyl Groups Impart to Di-Iron(I) Complex Aqueous Solubility and Stability, and Prominent Anticancer Activity in Cellular and Animal Models.

Using a multigram-scalable synthesis, we obtained nine dinuclear complexes based on nonendogenous iron(I) centers and featuring variable aminocarbyne and P-ligands. One compound from the series (FEACYP) emerged for its strong cytotoxicity in vitro against four human cancer cell lines, surpassing the activity of cisplatin by 3-6 times in three cell lines, with an average selectivity index of 6.2 compared to noncancerous HEK293 cells. FEACYP demonstrated outstanding water solubility (15 g/L) and stability in physiological-like solutions. It confirmed its superior antiproliferative activity when tested in 3D spheroids of human pancreatic cancer cells and showed a capacity to inhibit thioredoxin reductase (TrxR) similar to auranofin. In vivo treatment of murine LLC carcinoma with FEACYP (8 mg kg-1 dose) led to excellent tumor growth suppression (88%) on day 15, with no signs of systemic toxicity and only limited body weight loss.

HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus­Based In Vivo Prediction in Humans: Part II.

In part I, we reported Hansen solubility parameters (HSP, HSPiP program), experimental solubility at varied temperatures for TOTA delivery. Here, we studied dose volume selection, stability, pH, osmolality, dispersion, clarity, and viscosity of the explored combinations (I-VI). Ex vivo permeation and deposition studies were performed to observe relative diffusion rate from the injected site in rat skin. Confocal laser scanning microscopy (CLSM) study was conducted to support ex vivo findings. Moreover, GastroPlus predicted in vivo parameters in humans and the impact of various critical factors on pharmacokinetic parameters (PK). Immediate release product (IR) contained 60% of PEG400 whereas controlled release formulation (CR) contained PEG400 (60%), water (10%) and d-limonene (30%) to deliver 2 mg of TOTA. GastroPlus predicted the plasma drug concentration of weakly basic TOTA as function of pH (from pH 2.0 to 9). The cumulative drug permeation and drug deposition were found to be in the order as B-VI˃ C-VI˃A-VI across rat skin. This finding was further supported with CLSM. Moreover, IR and CR were predicted to achieve Cmax of 0.0038 µg/ mL and 0.00023 µg/mL, respectively, after sub-Q delivery. Added limonene in CR extended the plasma drug concentration over period of 12 h as predicted in GastroPlus. Parameters sensitivity analysis (PSA) assessment predicted that sub-Q blood flow rate is the only factor affecting PK parameters in IR formulation whereas this was insignificant for CR. Thus, sub-Q delivery CR would be promising alternative with ease of delivery to children and aged patient.

A spectrophotometric analysis of extracted water-soluble phenolic metabolites of lichens.

MAIN CONCLUSION: Rainwater most probably constitutes a relatively effective solvent for lichen substances in nature which have the potential to provide for human and environmental needs in the future. The aims were (i) to test the hypothesis on the potential solubility of lichen phenolic compounds using rainwater under conditions that partly reflect the natural environment and (ii) to propose new and effective methods for the water extraction of lichen substances. The results of spectrophotometric analyses of total phenolic metabolites in rainwater-based extracts from epigeic and epiphytic lichens, employing the Folin-Ciocalteu (F.-C.) method, are presented. The water solvent was tested at three pH levels: natural, 3, and 9. Extraction methods were undertaken from two perspectives: the partial imitation of natural environmental conditions and the potential use of extraction for economic purposes. From an ecological perspective, room-temperature water extraction ('cold' method) was used for 10-, 60-, and 120-min extraction periods. A variant of water extraction at analogous time intervals was an 'insolation' with a 100W light bulb to simulate the heat energy of the sun. For economic purposes, the water extraction method used the Soxhlet apparatus and its modified version, the 'tea-extraction' method ('hot' ones). The results showed that those extractions without an external heat source were almost ineffective, but insolation over 60- and 120-min periods proved to be more effective. Both tested 'hot' methods also proved to be effective, especially the 'tea-extraction' one. Generally, an increase in the concentration of phenolic compounds in water extracts resulted from an increasing solvent pH. The results show the probable involvement of lichen substances in biogeochemical processes in nature and their promising use for a variety of human necessities.

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron.

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.

Unleashing the Potential of ß -cyclodextrin Inclusion Complexes in Bitter Taste Abatement: Development, Optimization and Evaluation of Taste Masked Anti-emetic Chewing Gum of Promethazine Hydrochloride.

Motion sickness also known as kinetosis is a condition in which there exists a disagreement between visually perceived movement and the vestibular system's sense of movement. Nausea, vomiting, dizziness, fatigue, and headache are the most common symptoms of motion sickness. This study mainly focuses on the taste masking of Promethazine Hydrochloride (PMZ) by inclusion complexation method, its formulation development in the chewing gum form by using directly compressible gum base HIG® and its quality and performance testing. Different molar ratios (1:1, 1:2, 1:3 and 1:4) of PMZ-cyclodextrin complexes were prepared by using ß-Cyclodextrin (ß-CD) as a taste masking agent. These complexes were evaluated for FTIR, DSC, % Entrapment Efficiency, % drug yield, and taste evaluation by E-Tongue. The optimized ratio was further evaluated by sophisticated analytical techniques such as Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). A central composite design (CCD) (3 ^2) was utilized to examine the effects of independent variables (amount of gum-X1 and amount of plasticizer-X2) on dependent variables (%CDRY1 and hardness Y2). The prepared gums were evaluated for drug content, organoleptic properties, in-vitro dissolution testing by fabricated disintegration apparatus, texture analysis, etc. The optimization statistics showed that on decreasing the amount of gum, in- vitro drug release increases and hardness decreases. The optimized batch MCG-2 of Promethazine MCG showed 92.34 ± 0.92% of drug release, whereas for marketed formulation (Phenergan®-25 mg) drug release value was 86.19 ± 1.88%. Results provided evidence that PMZ MCGs could be a better alternative to conventional tablet formulations with improved drug release, palatability and texture.

[Preparation and performance evaluation of fast dissolving polymer microneedles piggybacked with sitagliptin].

The dramatic rise in the number of obese/overweight people is a global public health challenge that urgently requires novel and effective therapies. In this study, we designed a fast dissolving polymer microneedle array patch (SGN-PVP/PVA-MN) with sitagliptin as a model drug for treating obesity, focusing on the preparation process of the patch. We then characterized the morphology and dimensions of SGN-PVP/PVA-MN. Furthermore, we delved into the mechanical properties, solubility, skin-puncturing capability, and transdermal drug diffusion and release kinetics of SGN-PVP/PVA-MN. The results demonstrated that SGN-PVP/PVA-MN exhibited favorable morphology and mechanical properties, effectively penetrating the stratum corneum and creating microchannels for rapid transdermal drug diffusion. The in vitro transdermal diffusion assays revealed the release of 64.5% of the drug within 2 min and 95.7% within 10 min. With rapid dissolution and high drug diffusion efficiency, SGN-PVP/PVA-MN is poised to serve as an effective and safe treatment option for the individuals with obesity.

The influence of natural polymers on loratadine's solubility and dissolution profiles.

Second-generation tricyclic H1 antihistamine loratadine (LTD) has a high permeability, low water solubility, and an oral absorption rate dependent on the rate at which it dissolves in the gastrointestinal tract. One approach suggested for improving the drug's solubility and rate of dissolution is natural solid dispersion (NSD). The present study evaluated the use of hydrophilic natural polymers, sodium alginate (SA), hyaluronic acid (HA), and xyloglucan (XG), in natural solid dispersion to enhance LTD solubility and dissolution rate. A total of 12 formulations comprising varied drug-to-polymer ratios were produced and analyzed for percentage yield, water solubility, and in vitro dissolution rate. The solubility of LTD was improved in all formulations. Excellent results were achieved with NSD1 (LTD: SA 1:0.25), with a high yield (99%), superior solubility (0.187) compared to pure loratadine (0.0021), and a speedy dissolution rate (98%) within 30 minutes. These studies suggest natural polymers like SA, HA, and XG can considerably increase LTD solubility. When introduced into NSD, these polymers effectively augment LTD dissolving rates, presenting attractive prospects for better bioavailability and therapeutic efficacy.

Effect of ultrasonic activation on setting time, pH and calcium ion release, solubility, and chemical structure of calcium silicate sealers.

This study evaluated the setting time, pH, calcium ion release, solubility, and chemical structure of four calcium silicate sealers after ultrasonic activation (UA). Five sealers were evaluated: Sealer Plus (SP - control); Sealer Plus BC (SPBC), Bio C Sealers (BCS), Endosequence BC Sealer (EBC), and BioRoot RCS (BR). Ten groups were created based on the use or not of ultrasonic activation: SP; SP/UA; SPBC; SPBC/UA; BCS; BCS/UA; EBC; EBC/UA; BR; and BR/UA. Setting time was performed based on ISO 6876:2012 and ASTM C266-07 specifications. Solubility at 24hs, based on ISO 6876:2012. pH and calcium release were evaluated at 1, 24, 72, and 168hs. Raman spectroscopy was used to evaluate structural changes. Quantitative data were analyzed using One-Way ANOVA and Tukey post-hoc test (α=5%). Raman spectroscopy results were qualitatively analyzed. Setting times and solubility of all sealers were not affected by UA (p>0.05). The highest solubility was found for BCS, BCS/UA; and BR, BR/UA (p<0.05). After 24hs, calcium silicate sealers had higher pH than SP and SP/UA (p<0.05). BR and BR/UA had the highest pH at all time points. SP and SP/UA had stable pH at all time points. SP and SP/UA had the lowest calcium release values at all time points (p<0.05). EBC and EBC/UA calcium release significantly differ at 24,72 and 168hs (p<0.05). No chemical changes were observed during Raman spectroscopy. In conclusion, ultrasonic activation affected calcium ion release only for EndoSequence BC Sealer. Ultrasonic activation did not influence the initial and final setting time, solubility, pH, and chemical structure of any investigated sealers.