Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future for other poorly water-soluble drugs in which low bioavailability is a major concern.
The capacity of microwave non-destructive testing (NDT) technique to characterize the matrix property of binary polymeric films for use as transdermal drug delivery system was investigated. Hydroxypropylmethylcellulose (HPMC) and polyethylene glycol (PEG) 3000 were the choice of polymeric matrix and plasticizer, respectively with loratadine as the model drug. Both blank and drug loaded HPMC-PEG 3000 films were prepared using the solvent-evaporation method. These films were conditioned at the relative humidity of 25, 50 and 75% prior to physicochemical characterization using the established methods of ultra-violet spectrophotometry, differential scanning calorimetry and Fourier transform infrared spectroscopy methods, as well as, novel microwave NDT technique. Blank films exhibited a greater propensity of polymer-polymer interaction at the O-H domain upon storage at a lower level of relative humidity, whereas drug loaded films exhibited a greater propensity of polymer-polymer, polymer-plasticizer and/or drug-polymer interaction via the O-H, C-H and/or aromatic C=C functional groups when they were stored at a lower or moderate level of relative humidity. The absorption and transmission characteristics of both blank and drug loaded films for microwave varied with the state of polymer-polymer, polymer-plasticizer, and/or drug-polymer interaction of the matrix. The measurements of microwave NDT test at 8 and 12 GHz were sensitive to the polar fraction of film involving functional group such as O-H moiety and the less polar environment of matrix consisting of functional groups such as C-H and aromatic C=C moieties. The state of interaction between polymer, plasticizer and/or drug of a binary polymeric film can be elucidated through its absorption and transmission profiles of microwave.
A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with paracetamol as a model drug, filled into hard gelatin capsules and stored at three different temperatures for various lengths of time. The resultant solidified matrix within the capsule was subjected to thermal analysis using differential scanning calorimetry (DSC) to ascertain its supramolecular structure. Polymorphic transformations towards more stable gelucire forms were observed upon aging the matrices, with samples stored at a temperature near the melting range of the lower temperature gelucire melting fraction showing the most profound changes. The increase in the rate of drug release from aged samples could be correlated to the alterations to the supramolecular structure of the gelucire. Accelerated drug release from aged samples could also be seen from in vivo studies using healthy human volunteers, although the extent of absorption was not affected. Therefore, even though the sustainability of release may be compromised by aging the gelucire matrices, the bioavailability of the incorporated drug is unlikely to be affected.
The drug release characteristics of beads made of poly(methyl vinyl ether-co-maleic acid) using Zn2+ as the crosslinking agent were investigated with respect to the influence of microwave irradiation. The beads were prepared by an extrusion method with sodium diclofenac as a model water-soluble drug. They were subjected to microwave irradiation at 80W for 5 and 20 min, and at 300W for 1 min 20s and 5 min 20s. The profiles of drug dissolution, drug content, drug-polymer interaction and polymer-polymer interaction were determined by dissolution testing, drug content assay, differential scanning calorimetry and Fourier transform infrared spectroscopy. Treatment of beads by microwave at varying intensities of irradiation can aid to retard the drug release with a greater reduction extent through treating the beads for a longer duration of irradiation. The treatment of beads by microwave induced the formation of multiple polymeric domains of great strength and extent of polymer-polymer and drug-polymer interaction. The release of drug from beads was retarded via the interplay of O-H, N-H, C-H, (CH2)n and C-O functional groups of these domains, and was mainly governed by the state of polymer relaxation of the matrix unlike that of the untreated beads of which the release of drug was effected via drug diffusion and polymer relaxation. In comparison to Ca2+ crosslinked matrix which exhibited inconsistent drug release retardation behavior under the influence of microwave, the extent and rate of drug released from the Zn2+ crosslinked beads were greatly reduced by microwave and the release of drug from these beads was consistently retarded in response to both high and low intensity microwaves.
Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract, respiratory and skin infections in animals. However, low solubility and low bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is an inert, non toxic polymer with excellent hydrophilic properties, besides it can enhance bioavailability by forming drug polymer conjugates. With the aim of increasing solubility and bioavailability, enrofloxacin thin films were prepared using PVP as a polymer matrix. The obtained oral thin films exhibited excellent uniformity and mechanical properties. Swelling properties of the oral thin films revealed that the water uptake was enhanced by 21%. The surface pH has been found to be 6.8±0.1 indicating that these films will not cause any irritation to oral mucosa. FTIR data of the oral thin films indicated physical interaction between drug and polymer. SEM analysis revealed uniform distribution of drug in polymer matrix. In vitro drug release profiles showed enhanced release profiles (which are also pH dependant) for thin films compared to pure drug. Antibacterial activity was found to be dose dependent and maximum susceptibility was found on Klebsiella pneumonia making this preparation more suitable for respiratory infections.
In our previous study, a novel alginate-based bilayer film for slow-release wound dressings was successfully developed. We found that alginate alone yielded poor films; however, the addition of gelatine had significantly enhanced the drug dispersion as well as the physical properties. Here, an investigation of the drug-polymer interactions in the bilayer films was carried out. Drug content uniformity test and microscopy observation revealed that the addition of gelatine generated bilayer films with a homogenous drug distribution within the matrix. The FTIR and XRD data showed an increase in film crystallinity which might infer the presence of drug-polymer crystalline microaggregates in the films. DSC confirmed the drug-polymer interaction and indicated that the gelatine has no effect on the thermal behaviour of the microaggregates, suggesting the compatibility of the drug and excipients in the bilayer films. In conclusion, the addition of gelatine can promote homogenous dispersion of hydrophobic drugs in alginate films possibly through the formation of crystalline microaggregates.
Crystallinity plays a vital role in the pharmaceutical industry. It affects drug manufacturing, development processes, and the stability of pharmaceutical dosage forms. An objective of this study was to measure and analyze the carbamazepine (CBZ) crystallinity before and after formulation. Moreover, it intended to determine the extent to which the crystallinity of CBZ would affect the drug loading, the particle size, and the release of CBZ from the microparticles. The CBZ microparticles were prepared by encapsulating CBZ in ethyl cellulose (EC) polymer using a solvent evaporation method. EC was used here as a release modifier polymer and polyvinyl alcohol (PVA) as an aqueous phase stabilizer. Factorial design was used to prepare the CBZ microparticle formulations, including polymer concentration, solvent (dichloromethane, ethyl acetate), PVA concentrations factor, the homogenization time, and homogenization speed. The crystallinity of CBZ was calculated utilizing differential scanning calorimetry (DSC) thermal analysis. The crystallinity was calculated from the enthalpy of CBZ. Enthalpy was analyzed from the area under the curve peak of CBZ standard and CBZ-loaded microparticles. DSC and ATR-FTIR assessed the possible interaction between CBZ and excipients in the microparticle. The prepared CBZ microparticles showed various changes in the crystallinity rate of CBZ. The changes in the rate of CBZ crystallinity had different effects on the particle size, the drug loading, and the release of CBZ from the polymer. Statistically, all studied factors significantly affected the crystallinity of CBZ after formulation to microparticles.
For effective topical and transdermal drug delivery, it is necessary for most actives to penetrate and permeate through the stratum corneum (SC). Extensive investigation of the thermal behaviour of mammalian SC has been performed to understand the barrier function of the skin. However, little attention has been paid to the related experimental variables in thermal analysis of the SC using differential scanning calorimetry that may influence the results obtained from such studies. In this review, we provide a comprehensive overview of the thermal transitions of the SC of both porcine and human skin. More importantly, the selection and impact of the experimental and instrumental parameters used in thermal analysis of the SC are critically evaluated. New opportunities for the use of thermal analysis of mammalian SC in advancing skin research, particularly for elucidation of the actions of excipients employed in topical and transdermal formulations on the skin are also highlighted.
Star-shaped polymers have vast potential in bioapplication due to their architecture. In this study, the suitability of ring opening polymerization (ROP) technique to synthesis star-shaped poly(caprolactone) and the thermal properties of the synthesized star-shaped polymers were demonstrated. The 4 -arm star- shaped of poly(caprolactone) (4s PCL) with -OH terminal and average molecular weight (Mn) of 5000, 10000, and 15000 g/mol were synthesized via ROP of ԑ-caprolactone (ԑ-CL) using a symmetric pentaerythritol (PET) as the core. Different molecular weights were obtained by using different ratios of ԑ-CL and PET in the presence of catalyst, stannous octoate (Sn(Oct)2). The FTIR spectra showed the presence of bands of methylene group of polymer repeating chain which confirm ROP of the ԑ- caprolactone. The average molecular weight (Mn) determined from proton nuclear magnetic resonance (1H NMR) analysis showed that all 4s PCL have approximately the same molecular weight as the theoretical values. All polymers obtained had high yield with >85%. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis showed that there were no significance different in the thermal properties of the synthesized polymers. A single step degradation for all 4s PCL was observed and the crystallization melting point of the polymers was within the range of melting point of PCL.
The main purpose of this study was to analyzed and examined the cocoa butter samples from Sabah. This work presence the crystal phases present in cocoa butter sample thus proved the existence of polymorphs obtained from differential scanning calorimeter (DSC) analysis and confirmed by X-ray diffraction (XRD). The cocoa butter samples were extracted using a conventional method by Soxhlet Extraction method. Crystals were formed under controlled static and tempered conditions. Cocoa butter polymorphism demonstrates that it is the actual crystallization temperature, not the cooling rate that determines the polymorph that crystallizes.
Many attempts have been focused in the past on preparing of synthetic E-tricalcium (E-TCP), which being employed as bone substitute due to its biocompatibility and resorbability. Low temperature synthesize such as sol-gel method become popular due to the high product purity and homogenous composition. Sol-gel method is less economical towards commercialization because the cost of raw materials and the yield of the product that can be achieved. This paper describes the synthesis of ETCP via mixing of CaCO3 and H3PO4 followed by calcinations process at 750qC – 1050qC. X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), fourier transformation infra-red (FTIR) were used for characterization and evaluation of the phase composition, morphology, particle size and thermal behavior of the product. E-TCP phase start to occur after calcinations at 750qC.
We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as stabilizing polymers. Spray-dried amorphous indapamide, metolazone and glibenclamide crystallized via solution-mediated nucleation while glipizide suffered from solid-to-solid crystallization. The addition of 0.001%-0.01% (w/v) HPMC into the dissolution medium successfully prevented the crystallization of supersaturated solutions of indapamide and metolazone whereas it only reduced the crystallization rate for glibenclamide. Amorphous solid dispersion (ASD) formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did not completely eliminate the solid-to-solid crystallization of glipizide even though the overall dissolution rate was enhanced both in the absence and presence of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in the dissolution medium with higher solubility than the stable polymorph. As a complementary technique, molecular dynamics (MD) simulations of indapamide and glibenclamide with HPMC was performed. It was revealed that hydrogen bonding patterns of the two drugs with HPMC differed significantly, suggesting that hydrogen bonding may play a role in the greater stabilizing effect on supersaturation of indapamide, compared to glibenclamide.
The ability of palm oil (PO) to crystallize as beta prime polymorph has made it an attractive option for the production of margarine fat (MF). Palm stearin (PS) expresses similar crystallization behavior and is considered one of the best substitutes of hydrogenated oils due to its capability to impart the required level of plasticity and body to the finished product. Normally, PS is blended with PO to reduce the melting point at body temperature (37 °C). Lipid phase, formulated by PO and PS in different ratios were subjected to an emulsification process and the following analyses were done: triacylglycerols, solid fat content (SFC), and thermal behavior. In addition, the microstructure properties, including size and number of crystals, were determined for experimental MFs (EMFs) and commercial MFs (CMFs). Results showed that blending and emulsification at PS levels over 40 wt% significantly changed the physicochemical and microstructure properties of EMF as compared to CMF, resulting in a desirable dipalmitoyl-oleoyl-glycerol content of less than 36.1%. SFC at 37 °C, crystal size, crystal number, crystallization, and melting enthalpies (ΔH) were 15%, 5.37 μm, 1425 crystal/μm(2), 17.25 J/g, and 57.69J/g, respectively. All data reported indicate that the formation of granular crystals in MFs was dominated by high-melting triacylglycerol namely dipalmitoyl-oleoyl-glycerol, while the small dose of monoacylglycerol that is used as emulsifier slowed crystallization rate. Practical Application: Most of the past studies were focused on thermal behavior of edible oils and some blends of oils and fats. The crystallization of oils and fats are well documented but there is scarce information concerning some mechanism related to crystallization and emulsification. Therefore, this study will help to gather information on the behavior of emulsifier on crystallization regime; also the dominating TAG responsible for primary granular crystal formations, as well as to determine the best level of stearin to impart the required microstructure properties and body to the finished products.
Effects of phosphorus content (510 to 987 ppm) on the gelatinization and retrogradation of 6 potato cultivars (Benimaru, Hokkaikogane, Irish Cobbler, Konafubuki, Sakurafubuki, and Touya) were studied. Pasting properties were analyzed by RVA, thermal properties by DSC, and mechanical properties of the starch gels by TA. Phosphorus was positively correlated with swelling power (r= 0.84) and negatively correlated with solubility (r= 0.83). Phosphorus content showed significant effect on certain pasting properties of potato starch such as peak viscosity, breakdown, and setback. Phosphorus content showed a significant positive correlation with peak viscosity (r= 0.95) and breakdown (r= 0.90). Increasing concentration of phosphorus tends to decrease the setback. Phosphorus content had no influence on thermal properties and mechanical properties of potato starch gel.
Physicochemical properties of threadfin bream surimi with different levels of polydextrose (3%, 6%, 9% and 12%), raw surimi, raw surimi with addition sodium tripolyphosphate and commercial surimi (sucrose) during 6 months of frozen storage were investigated. The analyses included the measurement of Ca(2+)-ATPase, sulfhydryl contents, protein solubility, sodium dodecyl sulfate polyacrylamide gel electrophoresis, differential scanning calorimetry and scanning electron microscopy. The Ca(2+)-ATPase, sulfhydryl content and protein solubility levels added with 3%, 6%, 9% and 12% polydextrose can be maintained until the 6 months of storage by 47.33%, 41.60% and 51.41%, respectively. Differential scanning calorimetry showed decreases in thermal stabilization of myosin with regard to transition termperature. Analysis by scanning electron microscopy demonstrated that the number of pores formed was increased after storage. This study suggested that surimi stored with the polydextrose as a cryoprotectant was able to maintain physicochemical of surimi better compared to raw surimi with no additives or raw surimi with sodium tripolyphosphate.
The present study investigates the development of methyl cellulose (MC)-sodium alginate (SA)-montmorillonite (MMT) clay based bionanocomposite films with interesting wound healing properties. The differential scanning calorimetry analysis of the composite films revealed presence of single glass transition temperature (Tg) confirming the miscible nature of the ternary blended films. The increase in MMT ratio in the composite films reduced the mobility of biopolymer chains (MC/SA) which increased the Tg of the film. Thermogravimetric analysis showed that dispersion of clay (MMT) at nano level significantly delayed the weight loss that correlated with higher thermal stability of the composite films. It was observed that the developed films were able to exhibit antimicrobial activity against four typical pathogenic bacteria found in the presence of wound. The developed films were able to significantly inhibit (10 mg/ml) the growth of Enterococcus faecium and Pseudomonas aeruginosa. In vitro scratch assay indicated potential wound closure activities of MC-2-4 bionanocomposite films at their respective highest subtoxic doses. In conclusion, these ternary bionanocomposite films were found to be promising systems for wound healing applications.
Solid polymer electrolytes (SPEs) were prepared using rice starch as the polymer, sodium iodide (NaI) as the salt and 1-hexyl-3-methylimidazolium iodide (HMII) as the ionic liquid (IL). The solution casting technique was used for preparation of the PEs. The ionic conductivity and temperaturedependent properties of the PEs were measured and all the SPEs were found to follow the Arrhenius thermal activated model. Ionic conductivity increased as the percentage of ILs increased. The SPE containing 20% (wt) of HMII IL showed the highest ionic conductivity of 1.83×10-3 S/cm. Spectral and structural characterization of the PEs were performed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. The results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) indicate that the decomposition temperature (Tdc), glass transition temperatures (Tg) and melting points (Tm) shifted when complexation with HMII occurred. The PEs were used to fabricate dye-sensitized solar cells (DSSCs) and the DSSCs were analyzed under a 1-sun simulator. The SPE with the highest ionic conductivity displayed a short circuit current density (Jsc) of 9.07 (mA cm-2), open circuit voltage (Voc) of 0.58 (V), a fill factor (FF) of 0.65 and had the highest energy conversion efficiency of 3.42%.
A study was carried out to determine the physicochemical characteristics of the oil derived from papaya seeds of the Hong Kong/Sekaki variety. Proximate analysis showed that seeds of the Hong Kong/Sekaki variety contained considerable amount of oil (27.0%). The iodine value, saponification value, unsaponifiable matter and free fatty acid contents of freshly extracted papaya seed oil were 76.9 g I2/100g oil, 193.5 mg KOH/g oil, 1.52% and 0.91%, respectively. The oil had a Lovibond color index of 15.2Y + 5.2B. Papaya seed oil contained ten detectable fatty acids, of which 78.33% were unsaturated. Oleic (73.5%) acid was the dominant fatty acids followed by palmitic acid (15.8%). Based on the high performance liquid chromatography (HPLC) analysis, seven species of triacylglycerols (TAGs) were detected. The predominant TAGs of papaya seed oil were OOO (40.4%), POO (29.1%) and SOO (9.9%) where O, P, and S denote oleic, palmitic and stearic acids, respectively. Thermal analysis by differential scanning calorimetry (DSC) showed that papaya seed oil had its major melting and crystallization transitions at 12.4°C and -48.2°C, respectively. Analysis of the sample by Z-nose (electronic nose) instrument showed that the sample had a high level of volatile compounds.
A study was conducted to detect and quantify lard stearin (LS) content in canola oil (CaO) using differential scanning calorimetry (DSC). Authentic samples of CaO were obtained from a reliable supplier and the adulterant LS were obtained through a fractional crystallization procedure as reported previously. Pure CaO samples spiked with LS in levels ranging from 5 to 15% (w/w) were analyzed using DSC to obtain their cooling and heating profiles. The results showed that samples contaminated with LS at 5% (w/w) level can be detected using characteristic contaminant peaks appearing in the higher temperature regions (0 to 70°C) of the cooling and heating curves. Pearson correlation analysis of LS content against individual DSC parameters of the adulterant peak namely peak temperature, peak area, peak onset temperature indicated that there were strong correlations between these with the LS content of the CaO admixtures. When these three parameters were engaged as variables in the execution of the stepwise regression procedure, predictive models for determination of LS content in CaO were obtained. The predictive models obtained with single DSC parameter had relatively lower coefficient of determination (R(2) value) and higher standard error than the models obtained using two DSC parameters in combination. This study concluded that the predictive models obtained with peak area and peak onset temperature of the adulteration peak would be more accurate for prediction of LS content in CaO based on the highest coefficient of determination (R(2) value) and smallest standard error.
This study was to characterize the seed fat from Madhuca longifolia known as Mee fat and its solid and liquid fractions with the objective of distinguishing them. A sample of Mee fat was partitioned into solid and liquid fractions using acetone as the solvent medium. The isolated fractions were compared to the native Mee fat sample with respect to various physico-chemical parameters using standard chemical methods as well as instrumental techniques such as, gas liquid chromatography (GLC), reversed-phase high performance liquid chromatography (RP-HPLC), and differential scanning calorimetry (DSC). Basic analyses indicated that there were wide variations between the native sample and its fractions with respect to iodine value (IV), and slip melting point (SMP). The cloud point (CP) of the liquid fraction was found to be 10.5 degrees C. Fatty acid compositional analyses showed that the proportion of saturated fatty acids (SFA) such as palmitic and stearic went up in the high-melting fraction (HMF) while in low-melting fraction (LMF) the proportion of unsaturated fatty acid (USFA) such as oleic and lenoleic increased. According to the HPLC analyses, Mee fat had a tiacyl glycerol (TAG) sequence similar to that of palm oil. After fractionation, the solid and liquid fractions obtained were found to have TAG profiles very much different from the native sample. Thermal analyses by DSC showed that Mee fat had two-widely separated high and low melting thermal transitions, a feature which was beneficial for the effective separation of solid and liquid fractions. The thermal profiles displayed by the fractions were clearly distinguishable from that of the native sample.