Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases.

Psyllium arabinoxylan: carboxymethylation, characterization and evaluation for nanoparticulate drug delivery.

The objective of present investigation was to optimize the interaction between carboxymethylated psyllium arabinoxylan and chitosan to prepare polyelectrolyte naoparticles for drug delivery applications. Arabinoxylan extracted from psyllium was carboxymethylated by reacting with monochloroacetic acid under alkaline conditions. Carboxymethylation of psyllium arabinoxylan was observed to increase its crystallinity, improve thermal stability and decrease the viscosity. Further, the effect of concentrations of carboxymethylated arabinoxylan and chitosan on the particle size and particle size distribution of ibuprofen loaded polyelectrolyte nanoparticles was screened using two-factor, three-level central composite experimental design. The results of optimization study revealed that the formation of nanometric polyelectrolyte is favored at the median level of carboxymethylated arabinoxylan and chitosan concentration. The optimal concentrations of carboxymethylated arabinoxylan and chitosan were found to be 0.0779% (w/v) and 0.0693% (w/v) respectively, which provided polyelectrolyte particles of size 337.2 nm and polydispersity index 0.335. Further, polyelectrolyte complex nanoparticles were found to release ibuprofen over a prolonged period of 10h following Higuchi's square root release kinetics with the mechanism of release being combination of diffusion and erosion of matrix.

Thiol modification of psyllium husk mucilage and evaluation of its mucoadhesive applications.

Thiol functionalization of psyllium was carried out to enhance its mucoadhesive potential. Thiolation of psyllium was achieved by esterification with thioglycolic acid. Thiolation was observed to change the surface morphology of psyllium from fibrous to granular and result in a slight increase in the crystallinity and swelling. Thiolated psyllium was found to contain 3.282 m moles of thiol groups/g of the polymer. Mucoadhesive applications of thiolated psylium were explored by formulating gels using metronidazole as the model drug. On comparative evaluation thiolated psyllium gels showed 3-fold higher mucoadhesive strength than the psyllium gels as determined by modified physical balance using chicken buccal pouch. The results of in vitro release study revealed that thiolated psyllium gels provided a prolonged release of metronidazole. Further, the psyllium and thiolated psyllium gels were found to release the drug following first-order kinetics by combination of polymer relaxation and diffusion through the matrix.

Evaluation of tropicamide-loaded tamarind seed xyloglucan nanoaggregates for ophthalmic delivery.

The present study was aimed to prepare tamarind seed nanoaggregates and its evaluation for ophthalmic delivery. The preparation of tropicamide-loaded tamarind seed xyloglucan nanoaggregates was optimized using face centred central composite experimental design, employing the concentrations of tamarind seed xyloglucan and Poloxamer-407, as independent variables. The results revealed that concentration of TSX has a significant antagonistic effect on particle size, while poloxamer displayed a significant synergistic effect on encapsulation efficiency. The optimal concentrations of TSX and poloxamer were found to be 0.45% (w/v) and 0.5% (w/v) respectively. The optimized formulation of tropicamide-loaded TSX nanoaggregates showed a significantly higher corneal permeation of tropicamide across the isolated goat cornea compared to commercial conventional aqueous formulation. The results revealed excellent mucoadhesive properties of TSX nanoaggregates. Further, the tropicamide-loaded TSX nanoaggregates formulation showed excellent ocular tolerance and biocompatibility as determined by hen's egg test chorioallantoic membrane and resazurin assay on Vero cell lines.

Evaluation of mucoadhesive potential of gum cordia, an anionic polysaccharide.

The study involves mucoadhesive evaluation by formulating buccal discs using fluconazole as the model drug. The effect of compression pressure and gum cordia/lactose ratio on the ex vivo bioadhesion time and in vitro release of fluconazole was optimized using central composite experimental design. It was observed that the response ex vivo bioadhesion time was affected significantly by the proportion of gum cordia in the buccal discs while the in vitro release of fluconazole from the buccal discs was influenced significantly by the compression pressure. The optimized batch of buccal discs comprised of gum cordia/lactose - 0.66, fluconazole - 20 mg and was compressed at the pressure of 6600 kg. Further, it provided the ex vivo bioadhesion of 22 h and in vitro release of 80% in 24h. In conclusion, gum cordia is a promising bucoadhesive polymer.

Carboxymethyl gum kondagogu: synthesis, characterization and evaluation as mucoadhesive polymer.

The objective of the study was to modify gum kondagogu by carboxymethylation and to evaluate it for potential pharmaceutical applications. Carboxymethylation of gum kondagogu was carried out by reacting gum kondagogu with monochloroacetic acid under alkaline conditions. The results of characterization studies revealed that carboxymethylation of gum kondagogu increases its degree of crystallinity and surface roughness, reduces its viscosity and improves its mucoadhesive properties. Further, carboxymethyl gum kondagogu was explored for pharmaceutical applications by formulating ionotropically gelled beads using metformin as the model drug and calcium chloride as cross-linking agent. Ex vivo bioadhesion study conducted using isolated chick-ileum by wash-off test revealed bioadhesion of >80% over a period of 24 h. It was observed that increasing the concentration of cross-linking agent increases the % drug entrapment and reduces the release rate. The beads were found to release the drug by Fickian-diffusion mechanism and following zero-order release kinetics.

Stability studies on aqueous and oily ophthalmic solutions of diclofenac.

Various aqueous and oily diclofenac ophthalmic formulations were subjected to accelerated and long term stability studies. Degradation of diclofenac was found to follow first-order kinetics. Among the aqueous formulations containing preservative, formulation with PMA, PMN, SA, MP/PP and SMS showed diclofenac content above 90% after 6 months of accelerated and 12 months of room temperature storage. Diclofenac 0.1%, w/v aqueous formulation (pH 7.4), with 5-10% overages, containing SMS, MP/PP or PMN look promising taking both stability and corneal permeability in view. However, for use in cataract surgery formulation without preservative appears ideal. Oily ophthalmic formulations except those in olive and mustard oil, had more than 90% drug content after 6 months of accelerated and 12 months of room temperature storage. Diclofenac (0.2%, w/v) ophthalmic solution in sesame oil with 3% overage and containing benzyl alcohol (0.5%, v/v) as preservative, appears ideal, taking both stability and corneal permeability in view.

In vitro corneal permeation of diclofenac from oil drops.

In vitro transcorneal permeation of diclofenac from oil drops was studied using freshly excised goat cornea. The maximum apparent corneal permeability coefficient (Papp) was obtained with 0.2% (w/v) diclofenac drops in sesame oil followed by safflower oil, while formulation in castor oil provided minimal Papp. The addition of benzyl alcohol, a preservative, in oil drops, increased the Papp value of diclofenac. Partition experiments indicated increased partitioning of diclofenac in the aqueous phase in the presence of benzyl alcohol, and the same could be responsible for the benzyl alcohol-induced increase in Papp. The solubility of diclofenac was higher in castor, arachis, and sunflower oil. But drug permeation from 0.5-1.0% (w/v) diclofenac drops in castor oil or 0.5% (w/v) drops in arachis /sunflower oil was less than that observed with 0.2% (w/v) drops in sesame oil. Thus diclofenac 0.2% (w/v) drops in sesame oil containing 0.5% (v/v) benzyl alcohol provides maximum Papp. The formulation increased corneal hydration indicating corneal damage. Since corneal hydration is less than 83% the damage appears to be reversible. The saturation solubility of diclofenac in sesame oil at 4 degrees C is 0.33% (w/v). Hence diclofenac 0.2% (w/v) solution in sesame oil will not precipitate at 4 degrees C and therefore the chances of crystallization of diclofenac from the formulation due to climatic change leading to physical instability appear to be remote.

Effect of formulation factors on in-vitro permeation of diclofenac from experimental and marketed aqueous eye drops through excised goat cornea.

The effect of formulation factors on permeation of diclofenac from some experimental and marketed aqueous eye drops through excised goat cornea was evaluated. Raising the pH of formulation from 6.0 to 8.0 or diclofenac concentration from 0.05 to 0.15% (w/v) or adjusting tonicity with mannitol or addition of viscolizing agent decreased apparent permeability coefficient (Papp). Formulation (pH 7.4) containing sodium metabisulfite or EDTA or combination of methyl and propyl paraben showed significantly (p<0.05) higher Papp whereas benzalkonium chloride (BAC) had no effect and sorbic acid (SA) had reduced permeation. Surprisingly marketed drops containing BAC or SA, showed significantly (p<0.05) higher Papp and decreased in the order of Difen>Voveran>NSAID>Dicol>Diclolab. Lower pH (7.1-7.3) and surface tension of drops indicating presence of surfactant, could mediate increased permeation and presence of buffer could cause irritation on in vivo instillation. The marketed formulations showed corneal hydration >83% suggesting corneal damaging potential.