Differential Scanning Calorimetry Studies Research Articles

Solvent free Potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate 3D EMOF as thermally stable energetic material.

Heat-resistant explosives play a vital role in indispensable applications. For this, we have synthesized a novel, three-dimensional, solvent-free energetic metal-organic framework (EMOF) potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate (KDNODP) straightforwardly. The synthesized EMOF was characterized through IR, NMR spectroscopy, elemental analysis, and differential scanning calorimetry studies. Furthermore, single-crystal X-ray diffraction provided a complete description of KDNODP. It exhibits a three-dimensional EMOF structure with remarkably balanced properties such as high density (2.11 g cm-3), excellent thermal stability (291 ℃), good detonation performance (8127 m s-1 and 26.94 GPa) and low mechanical sensitivity (IS = 35 J; FS = 360 N) than the commonly used heat-resistant explosives HNS (density = 1.74 g cm-3; VOD = 7164 m s-1, DP = 21.65 GPa, IS = 5 J) as well as the similar reported energetic potassium MOFs. To gain insights into the packing and intermolecular interactions, the Hirshfeld surface and a 2D fingerprint analysis were examined. Additionally, scanning electron microscopy was used to investigate the particle size and morphological characteristics of KDNODP. These outcomes highlight a successful method for creating 3D EMOF based on a six-membered heterocycle as a potential heat-resistant energetic material.

Structure and Properties of Na2S-SiS2-P2S5-NaPO3 Glassy Solid Electrolytes.

In the development of sodium all-solid-state batteries (ASSBs), research efforts have focused on synthesizing highly conducting and electrochemically stable solid-state electrolytes. Glassy solid electrolytes (GSEs) have been considered very promising due to their tunable chemistry and resistance to dendrite growth. For these reasons, we focus here on the atomic-level structures and properties of GSEs in the compositional series (0.6-0.08y)Na2S + (0.4 + 0.08y)[(1 - y)[(1 - x)SiS2 + xPS5/2] + yNaPO3] (NaPSiSO). The mechanical moduli, glass transition temperatures, and temperature-dependent conductivity were determined and related to their short-range order structures that were determined using Raman, Fourier transform infrared, and 31P and 29Si magic angle spinning nuclear magnetic resonance spectroscopies. In addition, the conductivity activation energies were modeled using the Christensen-Martin-Anderson-Stuart model. These GSEs appear to be highly crystallization-resistant in the supercooled liquid region where no measurable crystallization below 450 °C could be observed in differential scanning calorimetry studies. Additionally, these GSEs were found to be highly conducting, with conductivities on the order of 10-5 (Ω cm)-1 at room temperature, and processable in the supercooled state without crystallization. For all these reasons, these NaPSiSO GSEs are considered to be highly competitive and easily processable candidate GSEs for enabling sodium ASSBs.

Development and Evaluation of Sulfobutylether-β-cyclodextrin Inclusion Complexes of Etoricoxib for Enhancing Dissolution

Introduction: Etoricoxib is a BCS class II drug with poor aqueous solubility and analgesic and anti-inflammatory properties. Complexation with cyclodextrins is one of the widely used methods, amongst others, for enhancing the solubility and bioavailability of drugs. In current research work, inclusion complexes of etoricoxib using modified forms of cyclodextrin, i.e., captisol were prepared using kneading, evaporation, and freeze-drying methods to improve the solubility and dissolution characteristics. Methods: Etoricoxib inclusion complexes (ratio 1:1) were formulated using kneading, evaporation, and freeze-drying methods. The formulated inclusion complexes were evaluated for phase solubility, equilibrium solubility studies, Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, differential scanning calorimetry studies, in vitro drug release, similarity factor and in vivo studies. Results: The freeze-drying method produced inclusion complexes with the highest equilibrium solubility (ten times that of the pure drug). Fourier transform infrared spectroscopy studies showed no drug-polymer interaction. Differential scanning calorimetry and scanning electron microscopy studies suggested the incorporation of the drug into inclusion complexes of cyclodextrin. In vitro dissolution studies of kneading, evaporation and freeze-drying method inclusion complexes showed 66.53%, 79.13% and 88% drug release, respectively, in 3h, whereas pure drug exhibited 61.77% drug release in 3 h. The f1 value obtained was less than 50, which is indicative of a significant difference in release characteristics of kneading, evaporation and freeze-drying methods with that of the marketed formulation. In vivo studies indicated that inclusion complexes formulated by the freeze-drying method showed better analgesic and anti-inflammatory effects in comparison to formulations prepared by kneading and evaporation methods. Conclusion: It is concluded that the formulation prepared by the freeze-drying method led to a significant enhancement of dissolution and solubility rate of etoricoxib in comparison to the formulation prepared by the kneading method and evaporation method.

Randomly Methylated β-Cyclodextrin Inclusion Complex with Ketoconazole: Preparation, Characterization, and Improvement of Pharmacological Profiles.

As a powerful imidazole antifungal drug, ketoconazole's low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated β-cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies. The complex was confirmed by FTIR (Fourier-transform infrared spectroscopy), DSC (differential scanning calorimetry), TGA (thermogravimetric analysis), SEM (scanning electron microscope images), and NMR (Nuclear magnetic resonance) studies. Through complexation, the water solubility of ketoconazole in the complex was increased 17,000 times compared with that of ketoconazole alone, which is the best result so far for the ketoconazole water solubility study. In in vitro pharmacokinetic studies, ketoconazole in the complex can be 100% released in 75 min, and in in vivo pharmacokinetic studies in dogs, through the complexation, the Cmax was increased from 7.56 μg/mL to 13.58 µg/mL, and the AUC0~72 was increased from 22.69 μgh/mL to 50.19 μgh/mL, indicating that this ketoconazole complex can be used as a more efficient potential new anti-fungal drug.

Enhancement in Dissolution Profile of Cilnidipine by Nanonization Technique: Optimization by Box-Behnken design

Objectives: Cilnidipine has limited 25-30% of bioavailability due to BCS class II category drug. The aim of present work was to improve the solubility followed by dissolution rate of cilnidipine by formulation of nanosuspension. Materials and Methods: The nanosuspensionwas developed usingnanoprecipitation techniqueaidingultra-sonication with solvent (Dimethyl sulfoxide), antisolvent (water) and stabilizer (polyvinyl alcohol). The nano formulation was statistically optimized using Design Expert software by theBox-Behnken design. The concentration of Poly Vinyl Alcohol, Volume of Antisolvent and Stirring Time were considered as independent factors whereas Particle size and polydispersity index were considered as dependent factors. Results: The particle size of nanosuspension was found 178.57nm with narrow polydispersity index of 0.130. The microscopy study confirmed amorphous nature particles with rough surface. The zeta potential of 4.55 ±2.78 for optimized formulation finds stability of formulation during storage. The differential scanning calorimetry study and X-ray diffraction pattern showed the crystalline cilnidipine drug was converted to amorphous form upon precipitation into nanoparticles. Due to the nanonization of cilnidipine, the dissolution profile was noted as 92.41±3.56% which was significantly improved as compared with plain drug release data. The stability data showed satisfactory result for 2 months. Conclusion: It is summarized that the nanoprecipitation technique with ultra-sonication is approaching method for the formulation of homogenous nanosuspension with uniform sized dispersion of cilnidipine. Therefore, it can be assumed that the upon the enhancement in dissolution rate, the cilnidipine loaded nanosuspension may lead to improved absorption of drug from intestine followed by significant improvement in bioavailability.

Oral pH triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part I: Optimization, in-vitro, and ex-vivo characterization

The primary goal of this research was to investigate pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLM) using Eudragit S-100 as a pH-dependent polymer. The formulation was optimized using the Box-Behnken design. The suggested C-SKLM formulation with the amount of ketoprofen = 189.09 mg, the amount of Eudragit-100 = 600 mg, and the paddle speed = 400 rpm showed a considerable particle size (106 µm), drug encapsulation efficacy (79.67%), and % cumulative drug release at 5th hr (8.62) and 10th hr (92.62) for oral administration. Microphotographs of scanning electron microscopy indicated that the optimized C-SKLM was smooth and spherical. The differential scanning calorimetry and X-ray powder diffraction studies have shown that ketoprofen was dispersed in the polymer in its optimized C-SKLM formulation, and the spectra from the Fourier transform infrared study have shown no significant drug-polymer interaction. Ex-vivo permeation studies on isolated rat gastro-intestinal segments revealed that the maximum amount of ketoprofen permeated after 2 h through the isolated stomach (0.559 ± 0.049 mg), small intestine (1.36 ± 0.226 mg), and colon (0.972 ± 0.068 mg) was observed for ketoprofen pure. In contrast, a significantly lesser amount of the drug was permeated through the stomach (0.1 ± 0.025 mg) and small intestine (0.28 ± 0.1 mg) than the colon (0.697 ± 0.23 mg) from the ketoprofen-loaded microspheres formulation. In-vitro and ex-vivo permeation studies suggest that the developed C-SKLM could be helpful for the effective management of early morning symptoms due to rheumatoid arthritis by delaying the release by targeting the colon.

Effect of Phosphorus-Nitrogen based Flame-Retardant Combined with Zinc Borate on Thermal Stability and Flame Retardancy of Epoxy Clay Nanocomposites

A phosphorus-nitrogen containing 6,6'-(piperazine-1,4-diyl)bis(6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide) (DOPO-PZ) flame-retardant was synthesized and its effect combined with zinc borate (ZnB) and nanoclay (NC) on thermal stability and flame retardancy of epoxy resin was studied. Various epoxy composites containing DOPO, DOPO-PZ, ZnB and NC using curing agent diaminodiphenylsulfone (DDS) were prepared. The X-ray diffraction (XRD) and transmission electron microscope (TEM) micrographs of the composites showed intercalated nanostructure of epoxy-clay nanocomposites. In thermogravimetric analysis (TGA), pure epoxy gave 3.4% char yield at 700 ºC in nitrogen atmosphere, while in case of EP/DOPO-PZ/ZnB/NC sample having 1% phosphorus content, 5 wt.% zinc borate (ZnB) and 3 wt.% nanoclay (NC), the char yield is increased to 24.0%. Differential scanning calorimetry (DSC) study showed decrease in the glass transition temperature (Tg) on the addition of flame-retardant due to plasticization effect and increase in Tg on addition of nanoclay due to formation of nanostructure of epoxy composites. The EP/DOPO-PZ/ZnB/NC nanocomposite sample exhibited a limiting oxygen index (LOI) value of 29.2% and passed the UL-94 test with a V-0 rating and thus achieved a sufficient flame retardancy.

Optimizing fluconazole-embedded transfersomal gel for enhanced antifungal activity and compatibility studies.

Fungal infections are of major concern all over the globe, and fluconazole is the most prevalently used drug to treat it. The goal of this research work was to formulate a fluconazole-embedded transfersomal gel for the treatment of fungal infections. A compatibility study between fluconazole and soya lecithin was performed by differential scanning calorimetry (DSC). Transfersomes were formulated by a thin-film hydration technique using soya lecithin and Span 80. A central composite design was adopted to prepare different formulations. Soya lecithin and Span 80 were chosen as independent variables, and the effect of these variables was studied on in vitro drug diffusion. Formulations were evaluated for entrapment efficiency and in vitro drug diffusion. The results of in vitro drug diffusion were analyzed using the analysis of variance (ANOVA) test. Optimized formulation was prepared based on the overlay plot and evaluated by scanning electron microscopy, DSC, vesicle size, polydispersity index (PDI), zeta potential, and in vitro drug diffusion studies. An optimized formulation was loaded into xanthan gum gel base and evaluated for pH, viscosity, in vitro and ex vivo drug diffusion, and antifungal activity. DSC studies revealed compatibility between fluconazole and soya lecithin. Entrapment efficiency and in vitro drug diffusion of various formulations ranged between 89.92% ± 0.20% to 97.28% ± 0.42% and 64% ± 1.56% to 85% ± 2.05%, respectively. A positive correlation was observed between in vitro drug diffusion and Span 80; conversely, a negative correlation was noted with soya lecithin. Entrapment efficiency, particle size, zeta potential, PDI, and drug diffusion of optimized formulation were 95.0% ± 2.2%, 397 ± 2nm, -38 ± 5mV, 0.43%, and 81 % ± 2%, respectively. SEM images showed well-distributed spherical-shaped transfersomes. In vitro, ex vivo drug diffusion and antifungal studies were conclusive of better diffusion and enhanced antifungal potential fluconazole in transfersomal formulation.

Inorganic-Organic Hybrid Layered Semiconductor AgSePh: Quasi-Solution Synthesis, Optical Properties, and Thermolysis Behavior.

Two-dimensional inorganic-organic hybrid layered semiconductors are actively studied because of their naturally formed multiquantum well (MQW) structures and associated optical, photoelectric, and quantum optics characteristics. Silver benzeneselenolate (AgSePh, Ph = C6H5) is a new member of such hybrid layered materials, but has not fully been exploited. Herein, we present a quasi-solution method to prepare high quality free-standing AgSePh flake-like microcrystals by reacting diphenyl diselenide (Ph2Se2) with silver nanoparticles. The resultant AgSePh microflakes exhibit room-temperature (RT) resolvable MQW-induced quasi-particle quantization and interesting optical properties, such as three distinct excitonic resonance absorptions X1 (2.67 eV), X2 (2.71 eV), and X3 (2.83 eV) in the visible region, strong narrow-line width blue photoluminescence at ∼2.64 eV (470 nm) from the radiative recombination of the X1 exciton state, and a large exciton binding energy (∼0.35 eV). Furthermore, AgSePh microcrystals show high stability under water, oxygen, and heat environments, while above 220 °C, they will thermally decompose to silver and Ph2Se2 as evidenced by a combination of thermogravimetry and differential scanning calorimetry and pyrolysis-coupled gas chromatography-mass spectrometry studies. Finally, a comparison is extended between AgSePh and other metal benzeneselenolates, benzenethiolates, and alkanethiolates to clarify differences in their solubility, decomposition/melting temperature, and pyrolytic products.

Development and Optimization of Proniosomal Formulation of Irbesartan Using a Box-Behnken Design to Enhance Oral Bioavailability: Physicochemical Characterization and In Vivo Assessment.

This research work aimed to develop and evaluate proniosomes for the oral delivery of the lipophilic drug Irbesartan (IRB) to improve its solubility and bioavailability. Proniosomes of Irbesartan were formulated using a lipid, surfactant, and carrier by a slurry method. Based on the prepared preliminary trial batches and their evaluation, the formulation was optimized by employing a Box-Behnken design (BBD) in which concentrations of span 60 (X1), cholesterol (X2), and mannitol (X3) were used as three independent variables and the vesicular size (VS) (Y1), % entrapment efficiency (% EE) (Y2), and % cumulative drug release (% CDR) (Y3) were used as dependent variables. The optimized batch B1 was obtained from the BBD experiment after validation of checkpoint analysis, and their characterization was done for VS, % EE, % CDR, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The optimized batch showed a VS of 199 ± 5.4 nm, a % EE of 99.25 ± 2.24%, and a % CDR of 97.36 ± 1.13% at 24 h. Scanning electron microscopy (SEM) study showed a smooth surface of batch B1. DSC and XRD studies indicated the amorphous nature of the proniosomal formulation. The proniosomal formulation showed increased solubility (2.65 ± 0.2 mg/mL) in phosphate buffer, pH 6.8, as compared to water (0.059 ± 0.02 mg/mL). The pharmacokinetic study in rats confirmed the increased bioavailability of the drug in optimized proniosomal formulation compared with its pure drug suspension. Cmax, Tmax, and AUC0-t of the drug also increased by 2-fold compared to those of drug suspension. Thus, in conclusion, the proniosomal formulation proved to be an efficient carrier for improved oral delivery of Irbesartan by improving the solubility and bioavailability of the drug.

Development and Evaluation of Venlafaxine Hydrochloride Tablets for Oral Drug Delivery Technology

Oral pills are the predominant, simple, and straightforward approach for administering drugs. The project’s primary goal is to create a pharmaceutical product that is equal in terms of its medicinal properties. A controlled-release version of the antidepressant venlafaxine hydrochloride was created and compared to the formulation currently available on the market. The launch of the branded product was assessed through an innovator and prototype evaluation. In order to develop stable and bioavailable dosage forms, it is necessary to gather pertinent data through preformulation testing. In order to create stable and bioavailable dosage forms, preformulation testing must be performed to gather relevant information among the several mixes, high-performance polymer copolymer K100M, ethyl cellulose, and cross-linked polyvinyl pyrrolidone 0.45%. The precise release mechanism could be determined by conducting in-vitro solubility tests on the created formulations and analyzing the results with a number of exponential equations. We used fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) studies to check if the polymers were compatible with the medicine.

Greenly building strong interactions between epoxy and carbon fiber fabric via vapor assisted ozone

AbstractTo enhance the performance of carbon fiber reinforced polymer (CFRP), it is crucial to establish robust interactions between epoxy and carbon fiber fabric (CFF). Herein, CFF was treated by an optimized H2O2/H2O/O3 oxidation method. The chemical and physical properties of the treated CFFs were meticulously characterized. For comparison, CFF, O3 treated CFF, and H2O/O3 treated CFFs were also examined. It was found that H2O2/H2O/O3 oxidized CFF more effectively than either O3 or H2O/O3. Reactive O groups were extensively grafted onto the surface of the H2O2/H2O/O3 oxidized CFF, leading to an increase in surface energy. Additionally, numerous defects were introduced on the surface of the H2O2/H2O/O3 oxidized CFF, significantly enhancing its surface roughness. Consequently, the interlaminar shear strength of H2O2/H2O/O3 oxidized CFF reinforced epoxy composite reached 63.31 ± 2.50 MPa, which is 43.3% higher than that of CFF reinforced epoxy composite. The fracture surface morphology and differential scanning calorimetry studies confirmed the presence of strong interfacial chemical interactions, while the increased surface roughness ensured robust interfacial physical interactions. Based on these findings, the mechanisms of the H2O2/H2O/O3 oxidized CFF reinforcing epoxy were proposed. The present work aims to give out some ideas for the fabrication of green and advanced CFRP.Highlights CFF was effectively oxidized by an optimized H2O2/H2O/O3 method eco‐friendly. Improved the interlaminar shear strength of the epoxy composite by 43.3%. Both the strong interfacial chemical and physical interactions were confirmed. The reinforcing mechanism is attributed to the robust interactions.

Quality by Design Based Development of Electrospun Nanofibrous Solid Dispersion Mats for Oral Delivery of Efavirenz

Poor aqueous solubility often results in poor dissolution behavior and, consequently, poor bioavailability for those drugs whose intestinal absorption is dissolution rate limited. It is essential for formulation scientists to identify strategies to improve the solubility and dissolution rate of candidate drugs in order to improve their bioavailability. The present study investigated electrospun polymeric nanofibers for efavirenz (an antiretroviral drug), a Class II drug in the Biopharmaceutical Classification System. In order to fabricate nanofibers, hydrophilic spinnable polymer like Soluplus was used. Statistical design of experiments was used to optimize electrospinning parameters. Scanning electron microscopy (SEM) studies confirmed the presence of nanofibrous material in the mat. The x-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies advocated the amorphization of efavirenz in the nanofiber samples. The optimized nanofiber-based platform significantly improved in vitro dissolution of efavirenz (89.0 ± 3.2% in 120 minutes) compared to pure efavirenz crystals (27.3 ± 2.4%).

Enabling a novel solvent method on Albendazole solid dispersion to improve the in vivo bioavailability

Albendazole, a vital medication endorsed by the World Health Organization for combating parasitic infections, encounters a challenge stemming from its low solubility, significantly impeding absorption and bioavailability. Albendazole has near-insolubility in most organic solvents, so the solid dispersions of albendazole were predominantly using the fusion method. However, the solvent method could offer the advantage of achieving molecular-level mixing homogeneity. In this investigation, we incorporated the pH adjustment to prepare albendazole solid dispersion using a solvent method, which utilizes trace amounts of HCl in methanol, yielding notably enhanced albendazole solubility. Subsequently, carriers such as PEG6000/Poloxamer 188 (PEG: polyethylene glycol) and PVP K30/Poloxamer 188 (PVP: polyvinylpyrrolidone) were employed to create albendazole solid dispersions. Comprehensive characterization through dissolution rate analysis, PXRD (Powder X-ray diffraction), SEM (Scanning electron microscopy), DSC (differential scanning calorimetry), and pharmacokinetic (PK) studies in mice and rats was conducted. The findings indicate that the solid dispersion effectively transforms the crystalline state of albendazole into an amorphous state, resulting in significantly enhanced in vivo absorption and a 5.9-fold increase in exposure. Besides, the exposure increased 1.64 times of commercial albendazole tablets. Notably, PEG6000/Poloxamer 188 and PVP K30/Poloxamer 188 solid dispersions exhibited superior dissolution rates and pharmacokinetic profiles compared to commercially available albendazole tablets.

The effect of poly(ethylene glycol) on the properties of poly (lactic acid)/silane-modified bacterial cellulose nanocomposites

ABSTRACT This study aimed to investigate the impact of poly (ethylene glycol) (PEG) on the properties of nanocomposites consisting of polylactic acid (PLA) and 3-aminopropyltriethoxysilane-modified bacterial cellulose (MBC) nanofibers. Differential scanning calorimetry (DSC) studies indicated that the presence of PEG enhanced the chain mobility of PLA during crystallization, thereby enabling the MBC to act as efficient nucleation agents. Furthermore, DSC and X-ray diffraction (XRD) analyses provided evidence for the formation of two distinct crystal structures, namely α and α,’ as well as various spherulitic dimensions. Finally, the toughening of PLA was occurred by adding PEG to PLA and ternary nanocomposites.

SOLUBILITY ENHANCEMENT OF ATAZANAVIR BY HYDROTROPIC SOLUBILIZATION TECHNIQUE

Objective: The present study aims to increase the solubility and dissolution of atazanavir sulfate (ATZ) by employing a hydrotropic solubilization technique. Methods: ATZ is a poorly soluble drug classified under the biopharmaceutical classification system (BCS)-II, which accounts for its poor oral bioavailability. Different hydrotropic agents, such as urea and sodium benzoate and their combinations at different ratios were prepared. The prepared hydrotropes were systematically investigated for compatibility between the drug and excipients using Fourier Transform Infra-Red Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) approaches. Further, in order to understand the conversion from crystalline to amorphous nature, X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies were also performed. The formulation of a mixed hydrotropic mixture comprising urea (2.5% w/v) and sodium benzoate (5% w/v) exhibited a 100.35±1.7 % drug release at 0.25 h with higher dissolution efficiency as compared with other batches of individual hydrotrope, mixed hydrotropes as well as pure drug. Results: FTIR studies revealed that there is no incompatibility between the drug and the selected hydrotropes. DSC studies also confirmed the fact that there is no interaction between the drug and the hydrotropes by the disappearance of an endothermic peak. XRD studies revealed that there was a significant reduction in the intensity of peaks, indicating the conversion of crystalline to the amorphous form. The SEM studies indicated that the drug appears crystalline in the shape of an irregular tiny prismatic needle, indicating its crystallinity. At the same time, the hydrotrope mixtures appeared in agglomerated form with a porous nature, which may be accountable for its increase in solubility. The hydrotropes prepared using urea alone exhibited an increase in solubility of 4.42 folds, and the hydrotrope prepared using sodium benzoate alone exhibited an increase in solubility of 3.178 folds; the combination hydrotropes of urea and sodium benzoate exhibited an increase in solubility of 8.78 folds in water as compared to pure drug. The drug release from the mixed hydrotropes obeys zero-order kinetics with diffusion as the main mechanism. Conclusion: The present investigation concluded that the combination of hydrotropes enhanced the solubility of the aqueous soluble drug ATZ. However, in vivo studies are essential to establish its potential effect.

Drug Polymorphism: An Important Pre-formulation Tool in the Formulation Development of a Dosage Form

Abstract: Polymorphism permits solids to have two or multiple crystal structures with varying orientations or conformations, and polymorph drug dissolution and solubility vary. Polymorphism influences drug efficacy, bioavailability and toxicity. Various parameters can regulate polymorph crystallization, including supersaturation phase, temperature, stirring rate, solvent addition rate, seed crystal, additives and pH. To characterize and monitor polymorphs, various analytical approaches are available, including powder X-Ray diffraction / X-Ray diffraction (PXRD/XRD), also called as Gold Standard method, differential scanning calorimetry (DSC), Infrared spectroscopy (IR), and microscopical studies. To prevent polymorphic change during production, distribution, and storage, formulation with the most stable form in the marketed product is considered. In addition, by monitoring each phase of raw material processing, polymorphisms can be controlled during dosage form manufacturing. The objective of this review is to provide concise information on drug polymorphism, their characterization process, their effect on the stability of dosage forms, factors controlling polymorphism in the crystallization process, some case studies on polymorphs, control of polymorphism during the formulation of successful dosage forms and some of the regulatory considerations regarding polymorphs. Various databases like Pubmed/Medline, Google Scholar and Web of Science of all English language articles were searched, and relevant information was collected regarding the importance of polymorphism in formulation development. From a vast literature survey, it was found that polymorphism is a very important tool in a pre-formulation study that provides information about the fate of a drug molecule in its journey. From the present study, it was concluded that the polymorphism property of a drug should be taken into consideration at the pre-formulation stage since it is a very important tool for the formulation of a successful dosage form with stability and efficacy.

Effect of SbCl5 Doping on the Electrical and Optical Properties of Polyamide Nylon 6 Films

Polyamide nylon 6 (PA6) films were fabricated using a solution casting method and the films were doped with SbCl5. The electrical conductivity increased with the dopant concentration due to the increase in formation of radical cations through the charge transfer from the isolated double bonds (–C=O–) in the polymer chains. The DC electrical conductivity reached a maximum of 0.01 S/cm for 0.5 ml SbCl5 doped films. Structural and optical characteristics of the pure and doped films were examined using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), X-Ray Diffraction (XRD), and Ultraviolet-Visible (UV-Vis) absorption spectra. The doped films exhibited discernible shifts in the optical band gap energy. The direct band gap values of PA6 films were reduced from 4.5 eV to 1.7 eV when doped with 0.5 ml SbCl5. ATR-FTIR spectral studies, and optical studies indicated the formation of charge transfer complexes with the amide group of nylon 6, resulting in the electrical conduction. The XRD studies disclosed the reduction in the crystallinity of the doped films. The thermal stability was studied using differential scanning calorimetry (DSC) and thermogravimetric analysis-derivative thermogravimetric (TGA-DTG) studies. The melting and crystallization temperatures were recorded from the DSC thermograms. The peak melting temperature of PA6 reduced from 217 °C to 186 °C for 0.5 ml SbCl5 doped films. The peak of crystallization observed at 182 °C for pure films was absent, for the doped samples. The peak degradation temperatures for both pure and doped samples were above 400 °C, revealing the thermal stability of both materials. The thermally stable, semi-crystalline and semiconducting polymer films, we suggest, would be suitable for optoelectronic applications.

Formulation, optimization and full characterization of mirtazapine loaded aquasomes: a new technique to boost antidepressant effects

Objective The development of Mirtazapine (MRT)-loaded aquasomes by co-precipitation sonication technique to boost the antidepressant potential of MRT. Methodology MRT-loaded aquasomes formulations were prepared using Box–Behnken design to investigate the effect of independent factors including sonication time (X1), sonication temperature (X2), and sugar concentration (X3) on the dependent variables as particle size and drug loading efficiency. The formulation of the optimized formula was verified by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Powder Diffraction (XRPD). Furthermore, the morphology of the formula was evaluated by Transmission Electron Microscopy (TEM). The optimum MRT- loaded aquasomes was assessed for physiochemical properties, in vitro MRT release and in vivo antidepressant effects in mice model. Results The results revealed that the optimized formula showed a small particle size of 202.7 ± 3.7 nm and a high loading efficiency of 77.65 ± 2.6%. Thermal DSC and XRPD studies demonstrated the amorphous nature of MRT-loaded aquasomes. The in vitro study demonstrated sustained release of F (opt) 88.16% after 8 h, compared with plain MRT release of 63.06% after 1 h. Mice treated with MRT-loaded aquasomes demonstrated reduced immobility time in behavioral analysis to 37% with MRT-loaded aquasomes, while plain MRT reduced it to 55%. Conclusion These results confirmed that the antidepressant effect of MRT was significantly boosted in formulated aquasomes, and thereby they provide a promising carrier nano vesicular system for effective delivery of MRT.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.