Arun T. Patil

Antidiabetic potential of unripe Carissa carandas Linn. fruit extract.

ETHNOPHARMACOLOGICAL RELEVANCE Carissa carandas commonly known as Karanda have a long history of use in traditional system of medicine. It is used by tribal healers of Western Ghat region of Karnataka as hepatoprotective and antihyperglycemic. However, no scientific data is available to validate the folklore claim. The present study has been designed to evaluate its unripe fruit for the antidiabetic activity. AIM In the present study, methanol extract of unripe fruits and its fractions were studied for its antidiabetic potential. MATERIALS AND METHODS The methanol extract and its fractions were screened for antidiabetic activity in alloxan induced diabetic rats. The polyphenolic, flavonoid and flavanone contents of methanolic extract and its fractions were also determined and correlated with its antidiabetic activity. RESULTS The experimental data indicated that the methanol extract and its ethyl acetate soluble fraction has significantly lowered the elevated blood glucose levels by 48% (p<0.001) and 64.5% (p<0.001) respectively at dose level of 400mg/kg per oral after 24h as compared to diabetic control. In order to assess the role of polyphenolic components in the relevant activity, polyphenolic and flavonoid contents were determined. The polyphenolic and flavonoid content of methanol extract and its ethyl acetate soluble fraction were found to be 15.8 ± 1.2mg and 18.55 ± 0.34 mg (gallic acid equivalent/g extract) and flavonoid content 2.92 ± 0.03 mg and 1.534 ± 0.30 mg (rutin equivalent/g extract) respectively. CONCLUSION The increased antidiabetic potential of ethyl acetate fraction over methanol extract is due to its partial purification achieved by fractionation which resulted in increase in degree of polymerization and segregation of secondary metabolites.

PEGylated rosin derivatives: Novel microencapsulating materials for sustained drug delivery

The aim of this study was to investigate PEGylated rosin derivatives (PRDs) as microencapsulating materials for sustained drug delivery. PRDs (D1, D2, and D3) composed of a constant weight of rosin and varied amounts of polyethylene glycol (PEG) 400 and maleic anhydride were synthesized in the laboratory. Microparticles were prepared by the O/O solvent evaporation technique using the acetone/paraffin system. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. The effect of the type of PRD, drug, PRD:drug ratio, viscosity of external phase, stirring speed, concentration of magnesium stearate (droplet stabilizer), and method of preparation on particle size, drug loading, and drug release profiles of microparticles was investigated. PRDs could produce discrete and spherical microspheres (with DFS) and microcapsules (with DLTZ). The drug loading value for microparticles was found to be in the range of 37.21% to 87.90%. The microparticle size range was 14 to 36 μm. The particle size and drug loadings of microparticles were substantially affected by the concentration of magnesium stearate and the type of drug, respectively. Most of the formulations could sustain the DFS and DLTZ release for 20 hours. DFS and DLTZ release from PRD microparticles followed Hixson-Crowell and first-order kinetics, respectively. The results suggest that PRDs can be used successfully to prepare discrete and spherical microparticles with DFS and DLTZ for sustained drug delivery.

Sustained Release Microspheres of Diclofenac Sodium Using PEGylated Rosin Derivatives

The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier () were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d90) ranged between 11–24 μm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size—small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n ∼ 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential

&NA; The apigenin‐phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design‐optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride‐induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design‐optimized levels of formulation and process variables. The physical‐chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36‐fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride‐elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid‐based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility. Graphical abstract Figure. No caption available.

Ketoprofen-loaded Eudragit RSPO microspheres: An influence of sodium carbonate on in vitro drug release and surface topology

Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by solvent evaporation technique using acetone-liquid paraffin (heavy) solvent system were examined. Depending upon polymer concentration in the internal phase, microspheres of particle mean diameter (122.8, 213.6 and 309.5 μm) were obtained. The influence of surface washing of microspheres with n-hexane, i.e. untreated microspheres (UM) on the drug content, drug release and surface topology of microspheres were compared to those of microspheres washed with sodium carbonate, i.e. treated microspheres (TM) in order to make the non-encapsulated surface drug soluble. The significant reduction in encapsulation efficiency (p < 0.001) and drug content (p < 0.001) after treatment, in combination with the small crystalline peaks observed during XRD testing and lack of melting endotherm observed in DSC testing, suggests that the washing process actually removes a significant amount of drug (p < 0.001) from the surface and encapsulated near to the surface of the microsphere polymer matrix. Scanning electron microscopy (SEM) examination revealed that the removal of surface drug did not affect the size of microspheres but the topology of treated smallest microspheres was modified. The ketoprofen release profiles were examined in phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In general both UM and TM result in biphasic release patterns, but the initial burst effect (first release phase) of TM was lower than that of UM. The second release phase did not change for the bigger size but increased for the smallest microspheres, probably owing to the modification of matrix porosity

A comparative study of aqueous and organic-based films and coatings of PEGylated rosin derivative.

Rosin was partially esterified with polyethylene glycol 400 and reacted with maleic-anhydride to form an ester-adduct derivative. Derivative and native rosin were characterized for physicochemical properties. Aqueous coating system of derivative was developed by ammonia neutralization method. Organic-based films were produced using acetone. Aqueous and organic-based films were comparatively evaluated. Derivative exhibited an excellent coat-forming ability on spherical-units. Aqueous-based film exhibited very high water vapor transmission rate, wettability, water uptake, and leaching at pH 6.8. A 20% w/w aqueous-based coat could sustain diclofenac sodium release for 8 h, whereas, 20% w/w organic-based coat released 20.11% of drug in 8 h. In conclusion, aqueous coating system of synthesized rosin derivative can be developed; however, aqueous-coats are less efficient to retard the drug release rate. Instead, the organic-based coatings can efficiently be used for sustained drug delivery.

Development and evaluation of a hot-melt coating technique for enteric coating

O revestimento enterico convencional requer o uso de polimeros orgânicos os quais sao igualmente danosos ao meio ambiente e ao pessoal que o executa. O revestimento por fusao a quente evita o uso de solventes e e processo mais seguro e que consome menos tempo. O presente estudo foi planejado para avaliar a eficacia do revestimento por fusao a quente (RFQ) como tecnica de revestimento enterico. Os peletes preparados por esferonizacao por extrusao foram selecionados como formulacao central para modelo de farmaco irritante gastrico, o diclofenaco sodico (DFS) em razao das vantagens inerentes sobre as formulacoes de unica dose. O acido estearico (AE) e o acido palmitico (AP) foram avaliados como materiais para o revestimento de fusao a quente. O RFQ foi realizado em recipiente especialmente modificado, aplicando AS e PA no estado fundido em peletes pre-aquecidos para atingir nivel de revestimento de 5 a 15% p/P. Os peletes revestidos por fusao a quente for avaliados quanto ao pH de desintegracao e a dissolucao in vitro na faixa de pH de 1,2 a 6,8, juntamente com base micromeritica. O SEM dos peletes revestido mostrou revestimento uniforme e plano. Esses resultados indicaram que o RFQ tanto do AE quanto do AP apresentou capacidade de revestimento muito boa. Os peletes revestidos mostraram pouca liberacao do farmaco em pH baixo. Como os peletes foram, subsequentemente, transferidos para pH mais altos, observou-se aumento gradual na liberacao do farmaco dos peletes com o aumento do pH do meio de dissolucao. A liberacao foi dependente da extensao do revestimento, sendo a liberacao enterica controlada, contrariamente a liberacao abrupta com cineticas mistas.

Conception and evaluation of sustained release polymeric matrix beads for enhanced gastric retention.

The present study was aimed at developing and evaluating polymeric beads with sustained drug release and prolonged gastric residence. The polymeric beads were prepared by solvent evaporation technique using Cellulose acetate (CA) as matrix former for model drug Ibuprofen (IBF) in 1% aqueous polyvinyl alcohol (PVA) solution as external phase. Effects of various formulation variables like drug-polymer ratio, external phase viscosity, external phase volume, solvent ratio and processing variables like stirring speed, temperature of external phase, stirring time, and drying temperature on properties of beads were accessed. Drug polymer ratio was optimized to maximize the percent yield and drug content. Beads were characterized for shape, size, percent buoyancy, entrapment efficiency, floating time and in-vitro drug release. The scanning electron micrographs show a porous nature of beads thereby enabling them to float. When used alone, CA though formed good beads, drug entrapment efficiency was very low. To increase the drug entrapment, CA was partially substituted with Ethyl cellulose EC (up to 20%) to modulate drug entrapment efficiency and optimize the bead properties including drug release. Beads formed with higher viscous solution either formed agglomerates or dumbbell shaped structures. The optimized batches have uniform size distribution, remained buoyant for more than 18 hours and sustained the drug release up to 10 hours with diffusion through matrix being the main drug releasing mechanism.

Formulation and in vitro evaluation of buoyant controlled release lercanidipine lipospheres

The aim of this study was to prepare and evaluate buoyant lipospheres containing lercanidipine hydrochloride. The lipospheres were prepared by modified melt dispersion technique using hydrophobic matrix of cetostearyl alcohol (CSA). The influence of formulation factors (stirring speed, lipid:drug ratio, lipid:surfactant polymer composition) on particle size, encapsulation efficiency and in-vitro release characteristics of lipospheres were investigated. The yields of all prepared formulation and encapsulation efficiencies were high for formulations which contain high lipid amount. The mean particle size significantly decreased (p < 0.001) by increasing the lipid:surfactant polymer and stirring speed (p < 0.001) of the system. Reduction in encapsulation efficiency (p < 0.001) and drug content (p < 0.001) was observed with increasing stirring speed and percentage of poloxamer 407 in formulation. Although lercanidipine hydrochloride release from Cetostearyl alcohol lipospheres were very slow and incomplete for all formulations f1–f6 (∼65% drug released in 12 h) and was increased (∼85% drug released in 12 h) in lipospheres formulations f7–f12, containing Poloxamer 407. Percentage of buoyant lercanidipine lipospheres of CSA (96–100% buoyancy up to 12 h) decreases (p < 0.001) with increasing percentage of poloxamer 407 and achieved the release profile suitable for peroral administration.

Formulation and Evaluation of Bilayered Gastroretentable Mucoadhesive Patch for Stomach-Specific Drug Delivery

The aim of the present work was to develop and evaluate stomach-specific controlled release, gastroretentable mucoadhesive patch of lercanidipine HCl. This drug is essentially soluble in gastric pH range of 1- 4 and have a partition coefficient (log p-value) of 6.1; according to this concept, it has been decided to formulate the gastroretentive bioadhesive patch. The patch system consisted of a drug release rate controlling film, using the combination of Eudragit RSPO and RLPO; mucoadhesive film by using the combination of various hydrophilic polymers. Bilayered patch were made by using the selected batch of two films using the layering method and evaluated for the various parameters like in vitro swelling study, ex vivo mucoadhesive strength. Film was folded into a hard gelatin capsule, evaluated for in vitro drug release in pH 1.2 containing 0.2% (w/v) sodium lauryl sulphate (SLS), and in vivo bioavailability in rabbits. Patches could control the drug release up to 12 h, having mucoadhesion strength in the range of 4.05±0.4 N to 4.52±0.12 N. In vivo bioavailability results indicate that the gastroretentive patch system provides a novel way to retain the drug matrix for the longer period of time in a stomach, enhance drug absorption and thereby offer a promising strategy for gastroretentive mucoadhesive drug delivery for the lercanidipine HCl.