Search

The immune system plays an important role in the prevention of infection and forms the first line of defense against pathogen attack. Delivering of antigen through mucosal route may elicit mucosal immune system as the mucosal surface is the most common site of pathogen entry. Mucosal immune system will be capable to counter pathogen at mucosal surface. Oral mucosal immunization opens the ways to deliver antigens at gut-associated lymphoid tissue. This can elicit both local and systemic immune response. Mucosal vaccines are economical, highly accessible, non parenteral delivery and capacity to produce mass immunization at the time of pandemics. To deliver antigens on the mucosal surface of the gastrointestinal tract, the immune system relies on specialized epithelial cell i.e. Microfold (M)-cell. An approach to exploit the targeting specific receptors on M-cell for entry of antigens has made a breakthrough in vaccine development. In this review, various strategies have been discussed for the possible entry of antigens through M-cells and an approach to increase the uptake and efficacy of vaccines for oral mucosal immunization.

Mucosal administration of vaccine can produce a strong immune response. Antigens adhere to “M-cells”, present at the intestinal mucosa and the M-cells produce immunity after actively transporting luminal antigens to the underlying immune cells. The objective of the present study was to prepare and characterize alginate coated chitosan nanoparticles (ACNPs) loaded with HBsAg as an antigen to produce immunity; additionally anchored with lipopolysaccharide (LPS) as an adjuvant. Ionic gelation method was used to prepare chitosan nanoparticles (CNPs) which were loaded with HBsAg and stabilized by alginate coating to protect from gastric environment. Results showed that the prepared LPS-HB-ACNPs were small and spherical with mean particle size 605.23 nm, polydispersity index 0.234 and Zeta potential −26.2 mV and could effectively protect antigen at GIT in acidic medium. HB-ANCPs were stable during storage at 4 ± 1 and 27 ± 2 °C. Anchoring with LPS showed increased immunity as compared to other formulations. Additionally, NPs elicited significant sIgA at mucosal secretions and IgG antibodies in systemic circulation. Thus, the prepared LPS anchored alginate coated chitosan NPs may be a promising approach as a vaccine delivery system for oral mucosal immunization.

This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol(®))/β-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena.Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-β-cyclodextrin complex has been prepared.Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution.Drug-cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone.

The present study was undertaken for characterization of the steady state and non steady state corneal permeation kinetics of diclofenac potassium (DCP) using statistical moment theory. Hydrogel films containing DCP in a hydroxypropyl methylcellulose (HPMC) matrix were prepared by a casting method, and the steady state and non-steady state corneal permeation parameters of diclofenac were evaluated using statistical moment analysis. The correlation coefficient (r), coefficient of non-determination and standard error of estimate (SEE) results indicated a good Level “A” correlation between in vitro dissolution and ex vivo steady state permeation of DCP from all the hydrogel formulations. SEM, XRD and DSC studies suggested the inhibition of the crystal growth and partial amorphization of diclofenac in the film. One way analysis of variance (ANOVA) followed by Dunnett's test revealed that all the hydrogel films containing plasticizer (L2, L3 and L4) show very high significant difference of extent of permeation in non-steady state (EPN), extent of permeation in lag time (EPL), extent of permeation in steady state (EPS) and total amount permeated in 360 min (TAP) from the control film containing no plasticizer (L1) related to highly improved permeation. Marked anti-inflammatory activity has been observed after application of the hydrogel film. The binding configuration of DCP-HPMC using docking calculations indicated drug–excipient interaction at the molecular level. Steady state and non-steady state corneal permeation parameters have been evaluated successfully using statistical moment analysis, and highly improved permeation has been observed when compared to the parameters of the film with the control.

Luliconazole (LZ), a poorly water soluble synthetic imidazole derivative is used in the treatment of fungal infections of skin. Hence, the investigation was aimed at formulating microemulsion based gels (MBGs) for solubilization of LZ as well as its better penetration for efficacious anti-fungal treatment. The solubility of LZ in various oils was investigated. Out of tried oils, olive oil exhibited highest solubility. Suitable combination of surfactants and co-surfactants were screened for selected oil to yield O/W type microemulsion. The Pseudoternary phase diagrams were developed to determine microemulsion existence area. The developed microemulsion was evaluated for particle size analysis, isotropicity, pH, drug content and rheology. Drug loaded microemulsion was slowly added to the viscous solution of 1 % Carbomer 934 under magnetic stirring to prepare MBG. The prepared MBG were evaluated in terms of their droplet size, spreadability, stability, in vitro permeation studies, and rheological properties. The phase study revealed that the maximum proportion of oil was incorporated in microemulsion systems when the surfactant-to-cosurfactant ratio was 3:1. The microemulsion was optimized with its components of Olive oil as oil, Capmul MCM as a surfactant and iso propyl alcohol as a cosurfactant. The globule size of the optimized batch was 32.59 nm. The MBG was non-irritant indicating their safety and was active against C. albicans indicating its efficacy. Short term stability study performed as per ICH guideline exhibited stable characteristic of developed formulation. Therefore, MBG of LZ is an efficacious treatment for fungal infections.

Kaolin can adhere to the mucosa and protect it by absorbing toxins, bacteria, and viruses. Ocular delivery and anti-inflammatory activity of dexamethasone hydrogel system could be advantageous after kaolin incorporation.Hydroxypropyl methylcellulose (HPMC) films of dexamethasone have been prepared without and with kaolin by solvent casting method. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were utilized for evaluating thermal property, crystallinity, and morphology of the film preparations respectively. In vitro drug release and corneal permeation ex vivo were carried out in phosphate buffer saline of pH 7.4 (PBS) at 34 ± 0.5°C for 6 h. Anti inflammatory effect of the prepared film was evaluated using carrageenan induced rabbit eye.Disappearance of melting endotherm in the DSC thermogram is the indication of almost complete amorphization of drug in all the films. High-intensity reflections with characteristic peaks of pure drug crystal have resulted extensively reduced ordering of the crystal lattice in the X-ray pattern of all the films. Photomicrographs revealed that the plate-shaped geometry of the drug crystal has almost been lost in absence and presence of the nano-kaolin particles in the films. Kaolin incorporation controlled the drug release up to 6 h. Ocular permeation was diffusion controlled and extended for 6 h or more without exhibiting significant "Burst effect". Adsorption of drug onto the surface of nano-kaolin prolonged the permeation due to cation exchange and hydrogen bonding. Signs of inflammation of the carrageenan induced rabbit eye have been disappeared almost completely after 2 h of film application.Local controlled delivery sustained anti-inflammatory activity of dexamethasone has been achieved using kaolin incorporated HPMC film.

Paracetamol exhibits poor compressibility, poor mechanical performance and very difficult to be tableted alone by direct compression method. In the present study compaction process of paracetamol has been characterized in the presence of microcrystalline cellulose (MCC) after talcum lubrication. Compressibility parameters under tapping related to apparent density were obtained by biphasic linear plots. Compacts were prepared over a compression pressure of 24.5 to 343.2 MPa, and change in apparent density and tensile strength was recorded. Primary rearrangement and the secondary rearrangement were the two major steps clearly observed during particle rearrangement process, and the primary rearrangement packing rate was found faster compared to secondary packing rate in all powder formulations. First step of packing compacted to a greater extent compared to the second step during the entire tapping process. Under applied pressure, density difference due to compaction by particle rearrangement was observed to be very high compared to compaction by plastic deformation in the formulations. Solid bridge formation and mechanical interlocking were found to be more intensified as the MCC amount increased with the consequent increase of mechanical strength of the formulation. Level A correlation has been established between tensile strength and apparent density change at the same pressure. Increased loading of MCC in the compacted tablet also increased drug dissolution.

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.

Effect of different hydrophilic plasticizers on drug crystallinity of hydroxypropyl methylcellulose (HPMC) matrix film was studied. HPMC films containing telmisartan using different plasticizers were prepared by casting method. Drug crystallinity in the films was examined using polarized light microscopy (PLM), scanning electron microscopy (SEM), and x-ray diffractometry (XRD) to describe their phase behavior/solid state miscibility/crystal growth and drug-polymer-plasticizer interaction. HPMC and plasticizer were compatible with the drug and no phase separation was observed upon solvent evaporation. Plasticized-HPMC contributed a major role in the significant inhibition of crystal growth of the drug in the film. The triethanolamine film produced a relatively smooth surface in comparison to the other films in the submicron level. The films have not shown any significant changes even after exposure to stress (40°C/75% RH, 6 w). Triethanolamine as plasticizer brought about amorphization of telmisartan to the maximum extent in the film which is technologically more advantageous than the others owing to its anticipated better bioavailability.

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.

The solvent evaporation of ibuprofen, Avicel, and Aerosil in selected ratios were evaluated for particle packing and rearrangement and drug release. Physicochemical characterization was carried out by using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Transitional tapping between primary rearrangement and secondary rearrangement was found to be 20–30 taps with native ibuprofen powder and up to 45 taps with all formulated powders. Particle packing in the rearrangement stage was increased for all the formulations with respect to ibuprofen alone. Combination of Avicel and Aerosil brought about partial amorphization of the drug and improved wettability after solvent evaporation. Significantly improvement of packing of ibuprofen in rearrangement stage has been achieved by solvent evaporation of ibuprofen, Avicel, and Aerosil, which brought about improved release of drug from all formulated tablets.

The in vivo assessment of percutaneous absorption of molecules is a very important step in the evaluation of any transdermal drug delivery system and a key goal in the design and optimization of transdermal dosage forms lies in understanding the factors that determine a good in vivo performance. The objective of the present investigation is to assess the in vivo performance of an optimized transdermal system of ondansetron hydrochloride in rabbits and to generate preclinical pharmacokinetic data. The pharmacokinetic performance of ondansetron hydrochloride following intravenous and transdermal administration was studied in rabbits following non compartmental pharmacokinetic analysis. The pharmacokinetic parameters such as area under the curve, elimination rate constant, elimination half life and mean residence time, were significantly (P < 0.01) different following transdermal administration compared to intravenous administration. Absolute bioavailability of the transdermal film studied was estimated to be 0.37 ± 0.06 which is quite low because a very high drug loading in the transdermal system was essential to achieve sufficient thermodynamic activity for transdermal permeation. Though in vivo studies in rabbits are found promising, investigations in healthy human subjects are essential to confirm the performance of the developed transdermal films.

Context: A nonoral alternative such as transdermal system is desired to improve bioavailability and to maintain a constant and prolonged drug level with reduced frequency of dosing. Objective: The objective of the investigation is to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the influence of chemical permeation enhancers (CPEs) on the percutaneous permeation pattern. Material and methods: A D-optimal mixture design was used to study the influence of CPE with oleic acid (OA), lauric acid, and propylene glycol (PG) as mixture components. The influence of chemical enhancers on skin permeation was compared using one-way analysis of variance followed by multiple comparison analysis. Criterion of desirability was used to optimize the therapeutic system. Preclinical studies in rabbits were also carried out to establish an ex vivo–in vivo correlation (EVIVC). Results: The drug permeation pattern suggested Higuchian diffusion as predominant mode followed by case II to super case II transport as drug transport mechanism. The optimized formulation was obtained using 5% (w/w) CPE consisting of a blend of 62.41% OA and 37.59% PG. About twofold increase in alfuzosin permeation was achieved with the optimized transdermal patch. An approximate linear EVIVC was established (R 2 = 0.971). Discussion: The optimized blend of enhancers could improve skin permeation parameters. A higher extent of in vivo skin permeation compared with cadaver skin permeation may be due to more permeable nature of rabbit skin. Conclusion: The investigations suggest an effective alternative delivery strategy such as transdermal systems for alfuzosin hydrochloride.

In the present investigation, controlled release gastroretentive floating drug delivery system of theophylline was developed employing response surface methodology. A 3(2) randomized full factorial design was developed to study the effect of formulation variables like various viscosity grades and contents of hydroxypropyl methylcellulose (HPMC) and their interactions on response variables. The floating lag time for all nine experimental trial batches were less than 2 min and floatation time of more than 12 h. Theophylline release from the polymeric matrix system followed non-Fickian anomalous transport. Multiple regression analysis revealed that both viscosity and content of HPMC had statistically significant influence on all dependent variables but the effect of these variables found to be nonlinear above certain threshold values.

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.

Ibuprofen was milled in the solid state with kaolin (hydrated aluminium silicate) in different ratio to examine the extent of transformation from crystalline to amorphous state. The physical stability of the resultant drug was also investigated. X-ray powder diffractometry (XRD) and birefringence by Scanning Electron Microscopy (SEM) studies indicated almost complete amorphization of the drug on ball milling with kaolin at 1:2 ratio. Fourier transform infrared spectroscopy (FTIR) data showed a reduction in the absorbance of the free and the hydrogen-bonded acid carbonyl peak of carboxylic acid group accompanied by a corresponding increase in the absorbance of the carboxylate peak, indicating an acid-base reaction between the carboxylic acid containing ibuprofen and kaolin on milling. The extent of amorphization and reduction in the carbonyl peak and increase in carboxylate peak was a function of kaolin concentration in the milled powder. On storage of milled powder (at 40 degrees C and 75% RH for 10 weeks), XRD and birefringence of SEM study showed the absence of reversion to the crystalline state and FTIR data revealed continued reduction of carbonyl peak, whereas, ibuprofen converted from its crystalline acid form to amorphous salt form on milling with kaolin. Kaolin-bound state of ibuprofen was physically stable during storage. In-vitro dissolution studies revealed that percent release of ibuprofen from the kaolin co-milled powder is in the order: 1:2>1:1>1:0.5>1:0.1>milled alone ibuprofen>crystalline ibuprofen.

This present study is a preliminary exploration of the affinity between a carboxylic model drug ibuprofen and aluminum hydroxide. Ibuprofen was comilled with aluminum hydroxide in different weight ratios in the solid state and was characterized by scanning electron microscopy (SEM), X-ray powder diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. XRD and SEM studies indicated complete interaction of ibuprofen with aluminum hydroxide and complete amorphization of aluminum hydroxide-ibuprofen complexed salt as well, on comilling with aluminum hydroxide at 1:2 ratio. FTIR data showed the disappearance of acid carbonyl peak with the appearance and the corresponding increase in absorbance of new signal at 1,682 cm(-1) in the 1:1 and 1:2 ibuprofen-aluminum hydroxide-comilled powder. The accompanied increase in the absorbance of carboxylate peak in the ibuprofen-aluminum hydroxide physical mixture, and 1:0.1, 1:0.5, 1:1, and 1:2 (IBA(pm), and IB(1)A(0.1), IB(1)A(0.5), IB(1)A(1), and IB(1)A(2), respectively) comilled powder indicated an acid-base reaction between ibuprofen and aluminum hydroxide. On storage at 40 degrees C and 75% relative humidity (RH) for 10 weeks, XRD study showed the absence of reversion to the crystalline state and FTIR data revealed continued increase of new signal at 1,682 cm(-1) relative to carboxylic acid peak and no reappearance of carboxylic acid peak. In vitro dissolution studies revealed that the percent release of ibuprofen from the aluminum hydroxide-comilled powder is in the following order: IB(1)A(2) < IB(1)A(1) < ibuprofen crystal < ibuprofen milled alone < IB(1)A(0.1) < IB(1)A(0.5). Aluminum metal cation might have interacted to form a complex through the carboxyl and carbonyl groups of ibuprofen. Improved dissolution of drug associated with IB(1)A(0.1) and IB(1)A(0.5) is because of the absence of a new signal at 1,682 cm(-1) and improved amorphization of the drug to some extent. Dissolution of drug affected in IB(1)A(2) and IB(1)A(1) may be because of the insoluble stable complex formation.

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.

This review focuses on the recent techniques of solubilization for the attainment of effective absorption and improved bioavailability. Solubilization may be affected due to cosolvent water interaction or altered crystal structure by cosolvent addition. Micellar solubilization could be affected by both ionic strength and pH. Addition of cosolvents to the surfactant solutions offers only a small advantage because of the decrease in the solubilization capacity of the micelles. Polymorphism is known to influence dissolution and bioavailability of the drugs. Molecular modeling study of cyclodextrin inclusion complexations can predict the inclusion modes, stoichiometry of the complex, and the relative complexing efficiency of cyclodextrins with various drug molecules.

The present study was designed to examine the larvicidal property of acetone leaf extracts of Annona reticulata L. ( A. reticulata ), (family: Annonaceae) against 1 st to 4 th instars larvae of three dreadful mosquitoes namely Aedes aegypti L., 1762 ( Ae. aegypti ), Anopheles stephensi Liston, 1901 ( An. stephensi ) and Culex quinquefasciatus Say, 1823 ( Cx. quinquefasciatus ). Cent percent mortality was observed at 12 ppm concentration in 1 st , 2 nd and 3 rd instars larvae of Ae. Aegypti , where as 9 ppm concentration showed 100% mortality in 1 st , 2 nd and 3 rd instars larvae of An. stephensi after 72 h of exposure. At 6 ppm concentration, 100% mortality was observed in 1 st instar larvae after 24 h of exposure and in 2 nd and 3 rd instars larvae of Cx. quinquefasciatus after 48 h of exposure. In the 72 h bioassay experiment, LC 50 and LC 90 values progressively decreased with the increase in exposure period, having the lowest values at 72 h of exposure. Among the three mosquitoes, Cx. quinquefasciatus proved to be most susceptible to acetone leaf extract of A. reticulata . Some non target organisms were found to be non-responsive to the bioactive extract when exposed. So, acetone leaf extract of A. reticulata was proved to be an efficient larvicidal agent against 3 important vectors like Ae. aegypti, An. stephensi and Cx. quinquefasciatus .

Present study was undertaken to evaluate the mosquito larvicidal potentiality of root extracts of Annona reticulata Linn. ( A. reticulata ), family Annonaceae against filarial vector Culex quinquefasciatus Say, 1823 ( Cx. quinquefasciatus ). Petroleum ether, hexane, and ethyl acetate root extracts of the plant were examined to established their larvicidal potentiality against 3 rd instar larvae of Cx. quinquefasciatus mosquito species. Crude and only ethyl acetate root extracts of the plant at different concentrations were examined on 1 st - 4 th instars larvae of Cx. quinquefasciatus . LC 50 value of ethyl acetate extract after 24 h of exposure against 3 rd instar larvae of Cx. quinquefasciatus were also examined on some non target organisms. Phytochemical analyses of the root extracts of A, reticulata were also investigated. 100% mortality were noticed at very low concentrations of petroleum ether, hexane, and ethyl acetate root extracts of A. reticulata against 3 rd instar larvae of Cx. quinquefasciatus . LC 50 and LC 90 values of ethyl acetate root extract was lower than petroleum ether and hexane root extracts after 24, 48, and 72 h of exposure. Crude and ethyl acetate root extracts showed excellent larvicidal activity against Cx. quinquefasciatus mosquito species. 100% mortality was observed at very low concentration for crude and ethyl acetate root extracts. LC 50 and LC 50 values gradually decreased with time of exposure for crude and ethyl acetate root extracts of A. reticulata . No mortality and sluggishness were observed in control experiments as well as on examined non target organisms. Phytochemical analyses of root extracts of the plant revealed the presence of different secondary metabolites. So crude and ethyl acetate root extracts of A. reticulata can effectively be used for larval mortality against Cx. quinquefasciatus mosquito species at a very low concentration.

One of the promising ways to reduce mosquito population is the use of larvicide. Curcuma aromatica is a cosmetic herb in South Asia . The present study was conducted to explore the larvicidal effect of Curcuma aromatica rhizome extracts against the Culex vishnui group. To assess the larvicidal activity, crude extracts of rhizome of Curcuma aromatica were prepared ranging from 0.02% to 0.1% concentrations against all the instars of Cx. vishnui larvae. Active fractions were obtained by using six different solvents i.e. petroleum ether, n-hexane, ethyl acetate, chloroform: methanol (1:1 v/v), acetone, and absolute alcohol from non-polar to polar fashion. All the solvent extractives were tested against all the larval instars with graded concentrations ranging from 20 ppm to 100 ppm. Through log–probit analyses, LC 50 and LC 90 values were determined. Afterwards the statistical justifications were done by ANOVA analyses with reference to time, concentrations and larval instars as three entirely randomized autonomous variables. Furthermore the bioactive fraction was tested against non-target organisms under laboratory conditions. Maximum mortality was recorded in 0.1% concentrations of crude rhizome extracts against all the instars. Ethyl acetate extractives were found to have good larvicidal effect only among all the solvent extractives. The LC 50 and LC 90 values of 3 rd instars larvae were 17.25 ppm and 78.02 ppm respectively after 72 h of post exposure.The non-responsiveness of the non-target populations towards extractives was also noticed. The rhizome extracts of Curcuma aromatica can be used as an alternative larvicide against the JE vector Cx. vishnui group.

The present study was undertaken to develop a suitable transdermal matrix patch of ketorolac tromethamine with different proportions of polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC) using a D-optimal mixture design. The prepared transdermal patches were subjected to different physicochemical evaluation. The surfacet opography of the patches was examined by scanning electron microscopy (SEM). The drug-polymer interaction studies were performed using Fourier transform infrared spectroscopic (FTIR) technique. A correlation between in - vitro drug-release and in - vitro skin permeation was established and the criterion of desirability was employed to optimize the formulation. The results of the physicochemical characterization and in - vitro permeation of the prepared patches were promising to formulate transdermal patches with PVP/EC combinations.

Ibuprofen is a poorly soluble and poorly compressible drug and is unsuitable for "direct tableting". Microcrystalline cellulose (Avicel(®) PH 101) based ibuprofen powder formulations have been comilled in presence of Aerosil(®) (colloidal silicon dioxide) as lubricant, and the total compression behavior was evaluated using the Cooper-Eaton equation. Scanning electron microscopy (SEM) revealed about the damage of crystal geometry of the crystalline drug after comilling. Differential scanning calorimetry (DSC) indicated decrease of melting endotherm (partially) attributing to the decrease in crystalline intensity of ibuprofen upon comilling. Small changes in the infrared spectra such as shift of characteristic bands, reduction in intensity, and appearance of new bands are mainly related to the possible physical interaction and/or amorphization of the drug in the comilled mixtures. Increased compaction can be achieved after milling of the microcrystalline cellulose based blends. Milling decreased particle size and improved wettability of the drug and increased dissolution. Microcrystalline cellulose based comilled ibuprofen powder with improved compression and dissolution may be taken as a future scope of scale up for "direct tableting".

The purpose of the present investigation is to assess the influence of casting solvent on crystallinity of ondansetron hydrochloride in transdermal polymeric matrix films fabricated using povidone and ethyl cellulose as matrix forming polymers. Various casting solvents like chloroform (CHL), dichloromethane (DCM), methanol (MET); and mixture of chloroform and ethanol (C-ETH) were used for fabrication of the transdermal films. Analytical tools like scanning electron microscopy (SEM), X-ray diffraction (XRD) studies, differential scanning calorimetry (DSC), etc. were utilized to characterize the crystalline state of ondansetron in the film. Recrystallisation was observed in all the transdermal films fabricated using the casting solvents other than chloroform. Long thin slab-looking, long wire-like or spherulite-looking crystals with beautiful impinged boundaries were observed in SEM. Moreover, XRD revealed no crystalline peaks of ondansetron hydrochloride in the transdermal films prepared using chloroform as casting solvent. The significantly decreased intensity and sharpness of the DSC endothermic peaks corresponding to the melting point of ondansetron in the formulation (specifically in CHL) indicated partial dissolution of ondansetron crystals in the polymeric films. The employed analytical tools suggested chloroform as a preferred casting solvent with minimum or practically absence of recrystallization indicating a relatively amorphous state of ondansetron in transdermal films.

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.

Nefopam hydrochloride, a nonsteroidal anti-inflammatory drug, is administered in tablet form three times daily or as intramuscular injection at 6-h intervals to treat disorders such as acute or constant pain. It is also used for a prolonged treatment of severe pain, when morphine therapy has to be withdrawn for morphine-related dependence. To achieve a constant drug-plasma level of nefopam for a prolonged period, a transdermal drug delivery system was fabricated in our present study by employing suitable experimental hydrophilic and lipophilic polymeric combinations of polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Physical studies including weight variation, moisture content, moisture uptake, flatness, external morphology of the formulations, and in vitro drug release were performed. Drug-excipient interaction studies were carried out using Fourier transform infrared spectroscopy. In vitro skin permeation study with cadaver skin was conducted using modified Keshary-Chein diffusion cells. Interactions between nefopam and PVP seem to contribute to the slow and controlled release pattern of nefopam. The scanning electron microscopy evaluation of prepared matrix patches revealed that drug was dispersed uniformly in polymeric matrix. In vitro drug release study showed that an increase in concentration of hydrophilic polymer, PVP, enhanced drug release substantially. In vitro skin permeation study showed variable permeation profiles of nefopam from the experimental patches. Among the formulations, PVP:EC (1:3) was found to provide slowest release and maximum sustained skin permeation of drug in vitro. Application of those patches, PVP:EC (1:3), on human volunteers was found to provide systemic availability of the drug till 48 h.

The present investigation aims at development of pressure sensitive adhesive (PSA) based drug in adhesive type transdermal systems of ondansetron hydrochloride with higher permeation flux. The effect of mixture of two chemical permeation enhancers (oleic acid and lauric acid diethanolamide); and drug loading dose on the ex vivo human cadaver skin permeation from the transdermal patches has been investigated using a d-optimal combined mixture design. Incorporation of chemical permeation enhancers significantly improved the permeability parameters and it was also found that blend of permeation enhancers is more effective than either permeation enhancer. Criterion of desirability was employed to numerically optimize the transdermal system. Optimized formulation was achieved with 67.5% lauric acid diethanolamide, 32.5% oleic acid and 10% drug loading in an acrylate based PSA matrix. Optimized formulation was found to be nonirritating and safe for dermatological application.

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.

The interaction pattern of gatifloxacin was temperature-dependent Langmuir isotherm, and the Langmuir coefficients increased as the temperature was raised. The perturbation experiment conducted on this system showed that the nature of interaction was irreversible. The enthalpy change is a positive value, indicating the existence of increased activation energy as the temperature is raised. The entropy value, 24.21 e.u. obtained in this system, indicated that the hydration shells of the ions were rather tightly bound. Intestinal permeation study also revealed the decreased bioavailability of gatifloxacin relatively to the presence of aluminium hydroxide. The strong adsorption of gatifloxacin by aluminium hydroxide is due to formation of complexes with cations of aluminium hydroxide through carboxyl and carbonyl groups of gatifloxacin.

Altered crystallization condition has been designed and adopted to a model non-steroidal anti-inflammatory drug, while crystallizing from ethanol-water solution in absence and presence of polymers such as Eudragit RS and ethylcellulose. To minimize the gastro-intestinal side effects nimesulide was considered as a model drug candidate for the development of suppository formulation. Physicochemical characteristics of the crystals were evaluated by Scanning Electron Microscopy (SEM). X-ray diffraction (XRD) and Fourier Transformed Infrared Spectroscopy (FT-IR). Smoothness and sharpness of the crystal have been decreased with increased concentration of a polymer. A little change in crystal habit and geometry has also been observed. Crystals are discrete in nature and more than 90% were in the range of 20-90 micron. The X-ray diffractions of nimesulide crystallized in absence of polymer and physical mixture of drug-polymer revealed fewer high intensity reflections when compared with the drug crystallized in presence of Eudragit RS, which testified a slight decreased ordering of crystal lattice in the latter. In presence of ethylcellulose, slightly increased ordering of crystal lattice was observed. No strong interactions were noticed as revealed by FT-IR spectroscopy. Drug dissolution rate from suppository formulations containing nimesulide crystallized in presence of polymer was found to delay as compared with the suppository prepared by nimesulide crystallized in absence of polymer.

The oral bioavailability of nalidixic acid (NA) is low due to its poor solubility and slow dissolution. Solid dispersions of NA containing varying concentrations of polyvinylpyrrolidone (PVP), beta-cyclodextrin (BCD) and sodium starch glycolate (SSG) were prepared by solvent evaporation technique in an attempt to improve dissolution rate of NA. Physical characterization of NA, physical mixtures (PM) and solid dispersions were investigated by a variety of analytical methods including scanning electron microscopy (SEM), infrared (IR) spectroscopy and powder X-ray diffraction (XRD). SEM was useful in the verification of possible nalidixic acid inclusion in the dispersion system by studying its surface and shape characteristics of different samples. IR analysis demonstrated no strong interaction between the drug and the carrier exists in the solid dispersions. The degree of crystallinity of nalidixic acid decreased and also differed with the dispersion systems of different carriers. Disolution studies indicated that the dissolution rate and percent dissolution efficiency (DE) were significantly increased in the solid dispersions compared with drug alone. The relative potency of the carriers to enhance the dissolution rate of nalidixic acid was in the order: BCDPVPSSG. The dissolution rate of the drug in the solid dispersions was faster when the ration of the drug to carrier was smaller. F-test suggests that first order model may be used for explaining the kinetics of drug release from all the solid dispersion systems.

Flurbiprofen loaded ethylcellulose micropellets with different drug loading were prepared by a quasi-emulsion solvent diffusion technique. Encapsulation parameters of micropellets such as actual drug loading, drug encapsulation efficiency (DEE) and loss of coating polymer (LCP) were determined. Actual drug loading was increased with the increased initial drug loading whereas encapsulation efficiency decreased with the increase of actual drug loading. In vitro drug release profiles of these micropellets were evaluated in distilled water (DW) and also in phosphate buffer solution (PBS) to indicate pH dependency release rates. All the batches of micropellets released about 35-59% in DW and 89-97% in PBS during the period of 8 h and the burst effect of about 50-75% in the first 1.5 h was seen only in PBS. The mechanism of release kinetics was evaluated by fitting the release data to the zero order, first order, Higuchi, Baker-Lonsdale and Peppas equations and also to the differential forms of zero order, first order and Higuchi model. Adequate fitting of release data was found with first order, Higuchi and Peppas models and hence these models were selected for F-test statistics for ascertaining the mechanism of drug release. Higuchi model of drug release in DW and PBS of all the formulations was ruled out due to its significantly different F-value with other models. Thus, mechanism of release of flurbiprofen from ethylcellulose micropellets may be explained by the diffusional exponent model of Peppas et al. as ascertained by F-test statistics rather than the same, based on some other diffusional models even though they have shown good correlation.