Ranks, Subdegrees and Suborbital graphs of the product action of Affine Groups

The action of affine groups on Galois field has been studied.  For instance,  studied the action of on Galois field for  a power of prime.  In this paper, the rank and subdegree of the direct product of affine groups over Galois field acting on the cartesian product of Galois field is determined. The application of the definition of the product action is used to achieve this. The ranks and subdegrees are used in determination of suborbital graph, the non-trivial suborbital graphs that correspond to this action have been constructed using Sims procedure and were found to have a girth of 0, 3, 4 and 6

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Analytical Investigation of the Possible Chemical Interaction of Methyldopa with Some Reducing Carbohydrates Used as Pharmaceutical Excipients

Purpose: Assessment of drug substance and excipients compatibility is an important issue during pre-formulation studies as well as the quality control of pharmaceutical dosage forms. In this study, potential incompatibility between methyldopa and reducing excipients was evaluated using physicochemical methods. Methods: Dextrose and lactose (anhydrous & monohydrate) were selected as reducing carbohydrates. The initial incompatibility was studied with DSC and FTIR on binary mixtures with 1:1 mass ratio. Results were confirmed using HPLC studies coupled with mass spectrometry. Results: The DSC curves indicated the elimination of the melting endotherm of methyldopa in the binary mixtures. A new peak at 1719 cm-1 was observed in the FTIR spectra that can be attributed to the loss of type one amine functionality. The m/z of the proposed compound was observed in the mass spectra. Conclusion: The potential incompatibility of Methyldopa with reducing carbohydrates was established using physicochemical methods

Recent advances in improving oral drug bioavailability by cocrystals

Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human

Tekućinsko-čvrsti pripravci kao sredstvo za evaluaciju i poboljšanje fizičkokemijskih svojstava teško topljivih lijekova

The potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (indomethacin) was investigated. In this study, different formulations of liquisolid tablets using different co-solvents (non-volatile solvents) were prepared and the effect of aging on the dissolution behaviour of indomethacin liquisolid compacts was investigated. To evaluate any interaction between indomethacin and the other components in liquisolid formulations, X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) were used. Dissolution test was carried out at two different pH, 1.2 and 7.2, to simulate the stomach or intestine fluid, respectively. The results showed that liquisolid formulations exhibited significantly higher drug dissolution rates at pH 1.2 and 7.2 compared to compacts prepared by the direct compression technique. The enhanced rate of indomethacin dissolution from liquisolid tablets was, due to an increase in wetting properties and surface area of drug particles available for dissolution. In order to investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the formulations were stored at 25 oC/75% relative humidity for a period of 12 months. The results showed that aging had no significant effect on dissolution profiles of liquisolid tablets. Liquisolid compacts containing propylene glycol as vehicle produced higher dissolution rates in comparison with liquisolid compacts containing PEG 400 or Tween 80 of the same concentration. The DSC and XPD results showed no changes in crystallinity of the drug and interaction between indomethacin and excipients (Avicel and silica) during the process.U radu je ispitivan učinak tekućinsko-čvrstih sustava na poboljšanje oslobađanja u vodi netopljivih tvari (indometacina). Koristeći različita nehlapljiva otapala pripravljeno je nekoliko tekućinsko-čvrstih tableta, a zatim je proučavan učinak starenja na oslobađanje indometacina. Moguće interakcije između indometacina i drugih komponenata praćene su difrakcijom rentgenskih zraka na praškastom uzorku (XPD) i diferencijalnom pretražnom kalorimetrijom (DSC). Oslobađanje je praćeno pri dva različita pH, 1,2 i 7,2, simulirajući uvjete u želučanoj ili crijevnoj tekućini. Rezultati pokazuju da je profil oslobađanja iz tekućinsko-čvrstih pripravaka značajno bolji pri pH 1,2 ili 7,2, u usporedbi s pripravcima dobivenim kompresijom. Poboljšanje oslobađanja indometacina iz tekućinsko-čvrstih pripravaka posljedica je povećanog vlaženja površine čestica ljekovite tvari. Da bi se proučio učinak starenja na čvrstoću pripravaka i oslobađanje ljekovite tvari, tekućinsko-čvrsti pripravci su uskladišteni 12 mjeseci na 25 oC/75% relativne vlažnosti. Rezultati ukazuju da starenje nema značajni učinak na profil oslobađanja. Pripravci s propilenglikolom imaju bolji profil oslobađanja nego pripravci s istom koncentracijom PEG 400 ili Tween 80. DSC i XPD pokazuju da nije došlo do promjene kristaliničnosti niti do interakcije između indometacina i pomoćnih tvari (Avicel i silikagel) za vrijeme izrade pripravaka

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD), particle size analyzer and differential scanning calorimetry (DSC). Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR) spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models

The use of various organic solvents to tailor the properties of Ibuprofen-glucosamine HCl solid dispersions

A fast release dosage form is desirable to improve the absorption of poorly water soluble drugs. Ibuprofen (IBU) is a BCS class II drug that exhibits poor dissolution rate in the gastrointestinal (GI) tract. The aim of the present study is to use various organic solvents to prepare solid dispersions of IBU in the presence of glucosamine HCl (GL), which acts as a carrier to enhance the dissolution of ibuprofen. Different ratios of ibuprofen and glucosamine were dissolved in various organic solvents to obtain the solid dispersions of ibuprofen-glucosamine mixtures. The physic-chemical/solid state analysis of the samples investigated using SEM, DSC, FT-IR and XRPD, particle size analysis and in vitro dissolution studies showed that the type of solvent has a big influence on the dissolution. Ibuprofen-glucosamine solid dispersions obtained from acetone produced better dissolution compared to that of other organic solvents. The effect of water in binary mixtures of acetone or ethanol was also investigated and the results showed that when the ratio of acetone to water was 75:25, the highest dissolution was obtained. Solid state analysis ruled out any chemical interaction between the dug and carrier even in the presence of various organic solvents which indicates a good stability of the solid dispersions to enhance the dissolution rate of ibuprofen. It was also investigated via XRPD analysis that the ibuprofen retained its crystallinity without any adverse effect on the dissolution rates