Search

The objective of the present work was to investigate the effect of various hydrophilic polymers, such as hydroxypropylmethyl cellulose, methyl cellulose, carboxymethyl cellulose and poly vinyl alcohol, on the in vitro dissolution property of ibuprofen (IBU) crystallized from aqueous polymeric solutions. By using the solvent-change technique, IBU crystal products were produced in the presence of the selected polymers. The results showed that in the presence of polymers, the crystallization yield of IBU was higher than that of pure drug crystals (absence of polymer). SEM photographs revealed visible changes in the crystal morphology in the presence of polymers. The FTIR spectra of the crystallized IBU (polymer-treated) showed a shift of the acid- -dimer peak from 1718 to 1721 cm-1 but the absence of specific peaks for polymers. An XRD study further confirmed the absence of polymers in the crystallized IBU as no specific peaks were observed for the polymers. A higher percentage of cumulative drug release was reported for the polymeric-treated IBU crystals than that of plain IBU. Further in vivo studies are warranted to establish the in vitro?in vivo correlation for future technology transfer of the formulation.

Crystal engineering is an integral part of the drug development research. Crystal forms can modify the physicochemical properties of the parent drug molecule. The present work was aimed at the synthesis and characterization of crystalline product of lamotrigine (LT), an U.S. Food and Drug Administration approved anti-epileptic drug, with citric acid (CA) to improve its release in gastric region and oral absorption. The crystalline products of LT?CA were developed by solvent evaporation method using ethanol-water as the solvent system. Appearance of new characteristic peaks in the FTIR spectra for the crystal products indicated formation of new crystal state. In DSC thermogram, melting point of the experimental crystal products was different than that of the pure drug. Further, formation of new crystalline phase was confirmed from XRD data through the identification of new sharp peaks for the selected crystal products. A higher cumulative percentage of drug release was observed for the crystal products than for the free drug within 60 min of drug release in simulated gastric fluid. However, in vivo studies are warranted for the future technology transfer of the product at industrial scale.

Budesonide, a glucocorticosteroid is generally used to treat chronic inflammation and asthma. Hepatic first-pass metabolism and poor solubility are the major causes of its limited oral bioavailability. Present work was undertaken for the preparation of hydrogel film formulation with cyclodextrin complexation of budesonide containing quaternary surfactant for possible enhancement of mucosal permeation. FTIR study confirmed drug-polymer hydrogen bonding. Almost complete amorphization of the drug was pronounced by SEM, DSC and XRD studies. The film containing benzalkonium and hydroxypropyl beta-cyclodextrin exhibited in vitro dissolution and mucosal permeation to the highest extent of 87.2 and 95.8 % respectively in contrast to the others. Film formed hydrogel in aqueous mucin and enhanced the mucosal tissue residence time due to the mucoadhesive nature of the polymer. Acute inflammation in the rabbit eye was controlled within 3 h by applying the film in the cul-de-sac. The presence of cyclodextrin and quaternary surfactant brought about significantly improved drug release and mucosal permeation compared to their absence in the HPMC film. Hydrogel formed in aqueous mucin enhanced the mucosal residence time and controlled acute inflammation in the rabbit eye within 3 h after topical application.

Carrageenan induced oxidative stress develops retinal damage and increases lipid peroxidation. Glycation of the lens proteins increases modified proteins and may affect the lens structural integrity and opacification, after increasing glucose concentration in the lens. Trimetazidine (TZ) has been reported to have cytoprotective anti-ischaemic activity after systemic administration in an animal model. Trimetazidine ophthalmic film formulation has been prepared using HPMC as the hydrogel-forming polymer. The cytoprotective role of trimetazidine has been studied on carrageenan-induced retinal damage of rat eye by histologicaland Malondialdehyde (MDA) assay applying sterilized film formulation. Trimetazidine solution was used in combination with a high concentration of glucose solution (55 mM) for examining the protective effect from cataract formation. Formulation showed controlled and extended ophthalmic permeation of the drug for about 5 h. Damage of retinal cells in the ganglionic layer has been decreased significantly in the trimetazidinetreated group. Drug treated control group also showed significant disappearance of pyknotic cells. The addition of trimetazidine to the glucose medium practically retarded the lens opacification by reducing the over-production of reactive oxygen species (ROS) in increased sugar concentration. Presence of trimetazidine probably decreased the drop of protein level in lens under stressed condition and greater preventive effect has been noticed with TZ concentration of 240 µg/ml rather than 120 µg/ml. Trimetazidine ophthalmic film formulation could prevent retinal damage and cataract formation.

Hydration behavior of hydrogel-based polymeric film possesses great importance in mucosal drug delivery. Modified Lag phase sigmoid model was used for the investigation of hydration of the film. Kaolin incorporated HPMC K100LVCR (HL) and K100M (HH) films containing dexamethasone as a model drug have been prepared for studying swelling kinetics. Swelling of HL and HH films was decreased with the gradual increase of kaolin content and HH of higher viscosity has shown higher value than HL matrix. Kaolin also inhibited the film erosion process. Mathematically modified lag phase sigmoid model demonstrated similarity of the predicted swelling content with the observed value. High R2 and small RMSE value confirmed the successful fitting of the modified lag phase sigmoid model to the experimental data of swelling content. τ value similar to the observed one was obtained. This modified model could be reliable enough for estimating hydration process in food grains, food packaging films etc.

Analysis of the binding interactions of ibuprofen and silicified-microcrystalline cellulose (SMCC) has been undertaken. Co-processing of ibuprofen with SMCC was carried out by solid state ball milling, and aqueous state equilibration followed by freeze drying to investigate the effect of silicified-microcrystalline cellulose on ligand. Molecular docking study revealed that ibuprofen formed complex through hydrogen bond with microcrystalline cellulose (MCC) and silicon dioxide (SiO 2 ); the binding energy between MCC and SiO 2 , and ibuprofen and SMCC were found as -1.11 and -1.73 kcal/mol respectively. The hydrogen bond lengths were varying from 2.028 to 2.056 A. Interaction of Si atom of SMCC molecule with Pi-Orbital of ibuprofen has shown the bond length of 4.263 A. Significant improvement in dissolution of ibuprofen has been observed as a result of interaction. Binary and ternary interactions revealed more stabilizing interactions with ibuprofen and SMCC compared to SMCC formation.

Titanium dioxide can adhere with human epithelial cells and have good tolerability. Present work has been undertaken to explore the influence of TiO2 on mucosal permeation of aceclofenac. Mucosal permeation of aeclofenac solution containing TiO2 has been carried out. In fourier transform infrared spectrosopy (FTIR), the intensity of the peaks has decreased along with the increase of TiO2 content in the formulation indicating a possible binding between drug and TiO2. Melting enthalpy has been decreased with the increased content of TiO2 in the solid. The status of crystal strain and dislocation density of TiO2 and aceclofenac in the solid state formulation has also been evaluated from Xray Diffraction data using Debye-Scherrer’s equation. Mucosal permeation of aceclofenac has shown sustained effect for more than 20 h in presence of titanium dioxide. Titanium dioxide could be used in designing formulation for sustaining mucosal aceclofenac delivery after performing risk assessment study.

Mucoadhesive type ocular film has been prepared for studying the anti-inflammatory potential of amlodipine (AML) on carrageenan-induced rabbit model and the effect of sulphobutyl-ether-beta-cyclodextrin on corneal permeation was tested. Hydroxypropyl methylcellulose (HPMC) ocular film was prepared after complexation of amlodipine with β-cyclodextrin, (BCD), hydroxypropyl β-cyclodextrin (HPCD), and sulfobutylether β-cyclodextrin (SBCD). The film without cyclodextrin showed a maximum swelling, and erosion to the highest extent. Both drug release and permeation were highly diffusion controlled and highest improvement was observed with SBCD due to increased dissolution, compared to other formulations with or without cyclodextrin. Highest binding energy and highest extent of amorphization were noticed in the SBCD film formulation. Improved amlodipine release in-vitro and ocular permeation were found by the HPMC film formulation after complexation of the drug with cyclodextrins wherein SBCD exhibited both to the highest extent. Binary and ternary systems molecular docking studies confirmed the lowest energy of binding between amlodipine and BCD compared to HBCD and SBCD. Signs of acute inflammation were mitigated within 2 h of film application in the cul-de-sac. Presence of sulphobutyl-ether β-cyclodextrin in the amlodipine-HPMC film can improve ocular permeation significantly and could be utilized as mucoadhesive type formulation for anti-inflammatory activity.

In this investigation, the effect of kaolin on hydration kinetics and swelling behavior of hydroxypropyl methylcellulose ocular film was studied. Gradual reduction in the extent of and rate of swelling of the film was noticed with increasing the content of kaolin. Peppas model revealed that the diffusion coefficient was increased in the presence of kaolin and also increased for the film of higher viscosity polymeric film. Peppas model suggested that the polymeric film followed the diffusion-controlled swelling mechanism. The Peleg rate constant was increased from 1.69 to 44.39 h/g indicating the initial water adsorption rate in the decreasing order while Peleg capacity constant did not vary significantly in the presence and absence of kaolin indicating lack of remarkable change of water adsorption capacity. The presence of kaolin in the film could maintain a safe corneal hydration level.

Assessment of interactions of ibuprofen and magnesium trisilicate after co-processing has been carried out by infrared spectroscopy. Dry-state ball-milling and, aqueous state kneading and freeze-drying were performed. FTIR spectroscopy of co-processed materials described acid–base reaction between the carboxylic acid containing ibuprofen to a significant extent. Increased absorbance of carboxylate peak accompanied by a consistently reduced absorbance of the carbonyl acid peak was evident. Absorbance of carboxylate peak was more in freeze-dried sample compared to milled product. Intermolecular hydrogen bonding between ibuprofen and magnesium trisilicate in the co-processed material has been suggested. Inhibition of crystal morphology has been noticed in the photomicrographs of both the products. DSC report has shown absence or significantly decreased melting endotherm representing almost complete amorphization of ibuprofen. Release of drug increased greatly after co-processing in comparison to crystalline ibuprofen. Freeze-dried samples have improved drug release more significantly compared to ball-milled samples.

The objective of this report was to evaluate the transcorneal permeation of diclofenac potassium (DCP) as a function of temperature from hydroxypropyl methylcellulose (HPMC) matrix film containing triethanolamine (TEM) as plasticizer and benzalkonium chloride (BKC) as preservative. Activation energy (Ea), enthalpy (ΔH), entropy (ΔS) and free energy (ΔG) of permeation, diffusion and partition were evaluated to understand the underlying mechanism of permeation. Permeation improved with the presence of both the plasticizer and preservative compared to preservative alone. Further, increased amount of TEM in the film increased drug transport across the cornea. Decreased Ea value of the film supported the fact. Rise of temperature from 26 to 30, 34 and 40 °C increased permeation in all the films. Ocular residence of the film in vivo in the rabbit revealed that the film swelled by pronounced lachrymal fluid uptake and traces of hydrogel remained still at the end of 6 h of application. Absence of characteristic exothermic peak of the drug in the thermogram of film formulations indicated the molecular dispersion of drug in polymer matrix. Scanning electron microscopy indicated that the drug crystal size decreased with increasing concentration of TEM in presence of BKC due to effective wetting of drug particles by the polymer.

Interaction and physicochemical characterization of dispersions of naproxen in calcium carbonate after freeze-drying the wet-state equilibrated mixture have been investigated by analytical methods. The FT-IR study revealed the acid-base reaction between naproxen and calcium carbonate. The DSC study indicated physical interaction and significantly diminished crystallinity of naproxen in the formulation containing higher quantities of calcium carbonate. Furthermore, the SEM study showed the reduced particle size and loss of crystalline morphology in the same sample. Drug release increased with the increase of calcium carbonate in the formulations. Formulation of naproxen with calcium carbonate in 1:2 ratio allowed its dissolution to the greatest extent (94.96%) while other compositions, 1:0.5 and 1:1, showed 80.86% and 78.30% release, respectively.

We have taken kinetic measurements of the hydrolytic degradation of cefixime, and have studied the effect of Captisol complexation and water-soluble polymers on that degradation. The phase solubility of cefixime in Captisol was determined. Kinetic measurements were carried out as a function of pH and temperature. High-performance liquid chromatography (HPLC) was performed to assay all the samples of phase-solubility analysis and kinetic measurements. Chromatographic separation of the degradation products was also performed by HPLC. FT-IR spectroscopy was used to investigate the presence of any interaction between cefixime and Captisol and soluble polymer. The phase-solubility study showed AL-type behaviour. The pH-rate profile of cefixime exhibited a U-shaped profile whilst the degradation of cefixime alone was markedly accelerated with elevated temperature. A strong stabilizing influence of the cefixime-Captisol complexation and hypromellose was observed against aqueous mediated degradation, as compared with povidone and macrogol. The unfavourable effect of povidone and macrogol may have been due to the steric hindrance, which prevented the guest molecule from entering the cyclodextrin cavity, whereas hypromellose did not produce any steric hindrance.

Different concentrations of crude and different solvents viz., n-hexane, ethyl acetate, and methanol fruit peel extracts of Citrus limetta Risso ( C. limetta ) were taken for investigation for larvicidal activity against Culex quinquefasciatus Say, 1823 ( Cx. quinquefasciatus ) mosquito species. Crude extract showed good larvicidal activity with very low concentrations against 1 st - 4 th instars larvae. Only 3 rd instar larvae were taken for larvicidal bioassay experiments for each solvent extract. LC 50 values of n-hexane, ethyl acetate, and methanol fruit peel extracts of C. limetta were 661.27, 1268, and 939.43 ppm respectively after 24 h of exposure. No mortality was observed on control treatments. Log probit analyses, regression equations, and R 2 values of larvicidal bioassay experiments with crude and different solvent extracts were determined. Statistical justification was done through ANOVA analyses. Qualitative phytochemical analyses were carried out and detected different secondary metabolites. No mortality was observed on tested non target organisms.

Crude, and three different solvents, viz., n- hexane, ethyl acetate, and methanol fruit peel extracts of Citrus maxima Merr. ( C. maxima ) were applied at dose dependent manner for larvicidal bioassay against Culex quinquefasciatus Say, 1823 ( Cx. quinquefasciatus ) mosquito. All instars larvae were used for larvicidal bioassay of crude fruit peel extract and only 3 rd instar larvae were used for larvicidal bioassay of different solvent extracts. Log-probit analyses along with Regression equations and R 2 values were determined for larvicidal activity of both crude and different solvent extracts. An ANOVA analysis was carried out to justify the statistical significance. Qualitative phytochemical analyses were done. n-Hexane fruit peel extract was also applied on non target organisms. Crude fruit peel extract of C. maxima showed strong lethal activity against all instars larvae of Cx. quinquefasciatus . 1 st instar larvae were most susceptible to crude fruit peel extract. 1 st instar larvae showed 100% mortality only at 0.2% concentration of crude fruit peel extract after 72 h of exposure. 100% mortality of 3 rd instar larvae were observed at 400 ppm concentration of n-hexane fruit peel extract after 24 h of exposure whereas, ethyl acetate and methanol fruit peel extracts showed 100% mortality at 800 ppm concentration after 72 and 24 h of exposure respectively. LC 50 values of n-hexane, ethyl acetate and methanol fruit peel extracts were 204.60, 640.95, and 336.36 ppm, respectively against 3 rd instar larvae after 24 h of exposure. No mortality was observed on control treatments. Fruit peel extract contained different phytochemical constituents. Non-target organisms did not show any abnormal activity and mortality.

Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability) of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A) and malonic acid based aspirin effervescent tablet (Product B) formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24), permeation flux (J) and steady state permeability coefficient (P SS) were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.