Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

Study Of The Anti-Hyperlipidemic Effect Of The Combined Administration Of Three Natural Extracts In A Poloxamer-407 Hyperlipidemic Model And Their Lc-Esi-Ms/Ms2 And Hplc Profiling

Objective: Dyslipidaemia is considered a high-risk factor for inducing atherosclerosis and cardiovascular diseases (CVDs). This study aims to investigate the anti-hyperlipidemic effect of the co-administration of the ethanol extracts of both ginger (root and rhizome) and leek (leaves and bulbs) in addition to the aqueous extract of gum arabic.  Methods: Rats were divided into eight groups: Hyperlipidaemia was induced in rats by a single intraperitoneal injection of Poloxamer 407 (P-407) [1 g/kg], negative control [saline injected], hyperlipidemic control [P-407 injected], positive control [Atorvastatin 70 mg/kg], groups four, five and six received ginger extract (400 mg/kg), leek extract (500 mg/kg) and gum arabic aqueous extract (7.5 g/kg) respectively and groups seven and eight received a co-administration of ginger, leek and gum arabic extracts at doses A and B respectively. Lipid profile was monitored. The profiling of all the tested extracts was performed by LC-ESI/MS and HPLC. Results: A significant anti-hyperlipidemic activity (P<0.05) was seen for group eight among all the tested groups producing ≈54%, 72%, 50% and 72% decrease in the measured parameters total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) respectively. An overall of 56 and 45 compounds were tentatively identified in the ethanol extracts of ginger and leek, respectively. Galactose and arabinose sugars were found to be the major saccharides in gum arabic and glucuronic acid was the major polyuronide part. Conclusion: the co-administration of a group of natural extracts in the given concentration proved to be more effective than the use of synthetic drugs or the use of a single component.

Formulation Optimization of Citalopram Hydrobromide Thermosensitive Nasal Gel and Its In Vitro Properties / 中国药学杂志

OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.

Metronidazole thermogel improves retention and decreases permeation through the skin

ABSTRACT Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects.

Preparation and in Vitro Properties of Paeonol Thermo Sensitive Gel / 世界科学技术-中医药现代化

This study aimed at preparing paeonol thermosensitive gel and preliminary exploring its properties in vitro.Tube inversion method was adopted to investigate the effects of concentrations of poloxamer 407 and poloxamer 188 on gelation temperature.Then,viscosity of the gel was detected by rotary viscometer,and in vitro erosion and drug release characteristics of the gel by no film stripping method.As a result,the gelation temperature of poloxamer 407 decreased with the increase of its concentration,while gelation temperature of poloxamer 407 increased with the accelerating concentration of poloxamer 188.The cumulative drug release of paeonol thermo sensitive gel was up to 70％ in 320 rin.Gel dissolution and drug release were simultaneously performed without burst release phenomenon.It was concluded that the preparation process of paeonol thermo sensitive gel was simple and easy to use with the overt effect of sustained-release.

Poloxamer 407 Hydrogels for Intravesical Instillation to Mouse Bladder: Gel-Forming Capacity and Retention Performance

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

retention of poloxamer-basedhydrogels for vaginal application in mouse and rat models

The purpose of this study is to evaluate theretention capabilities of poloxamer-basedhydrogels for vaginal application with nonoxinol-9 as the model drug. Twohydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties,hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing withTc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32 °C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared, GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate thehydrogel for vaginal application.

Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery.

Ophthalmic formulations in terms of eye drops are more frequently used formulation for ocular disorders. But unfortunately this mode of drug instillation into the cul-de-sac of eye shows very poor ocular bioavailability (less than 5%). A large number of carrier systems have been investigated to overcome this problem. In the present study a novel nano-carrier system (Ketorolac loaded cubosomes) is developed and evaluated for the safe and enhance ocular bioavailability. Cubosomes were developed and optimized by utilizing glyceryl mono-oleate, poloxamer 407 and initial drug concentration. Finally developed formulation was evaluated for various In vitro characteristics i.e. particles size, size distribution, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, and ocular tolerance study. The optimized drug loaded cubosomal formulation showed mean particle size, polydispersity index, and entrapment efficiency 127.3±12.23 nm, 0.205±0.011, and 53.27±5.23 %, respectively. Transmission electron microscopic analysis revealed a cubic shape of developed formulation. Further, developed formulation exhibited biphasic release profile. Significant high transcorneal permeation (2.07 folds) and corneal retention (2.24 folds) of ketorolac was observed with cubosomal formulation correspond to Ketorolac solution (p< 0.01). Further safety profile of optimized formulation was evaluated by histopathology of corneal membrane. The developed novel ocular carrier system (cubosomes) might be a promising platform as a vehicle for effective ocular drug delivery.

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line.

O ácido ursólico é um candidato promissor para o tratamento da doença de Chagas, contudo este fármaco possui baixa solubilidade aquosa e limitada absorção intestinal, ambos os fatores limitantes da biodisponibilidade. Entre as estratégias para potencializar a solubilidade e a dissolução de fármacos lipofílicos, as dispersões sólidas estão crescendo em popularidade. Neste estudo, empregamos mistura dos tensoativos, poloxamer 407 e caprato de sódio, para produzir dispersão sólida contendo ácido ursólico, com o objetivo de aumentar tanto a dissolução do fármaco quanto a atividade tripanocida in vivo. Comparada à mistura física, a dispersão sólida apresentou maior densidade e menor tamanho de partícula. Os resultados da análise de espectroscopia no infravermelho com transformada de Fourier mostraram interações intermoleculares do tipo ligações de hidrogênio entre o fármaco e o poloxamer 407. Os experimentos de difratometria de raio-X revelaram a conversão do fármaco de sua forma cristalina para a forma amorfa, mais solúvel. Consequentemente, a solubilidade do ácido ursólico em dispersão sólida foi aumentada e o fármaco dissolveu-se de maneira mais rápida e completa. Em conjunto com as propriedades promotoras de absorção oral do caprato de sódio, estes resultados explicaram o aumento da atividade tripanocida in vivo do ácido ursólico em dispersão sólida, que também se provou segura após avaliação de citotoxicidade empregando a linhagem celular LLC-MK2.

Preparation and Dissolution Rate in vitro of Idebenone Solid Dispersion / 中国药房

OBJECTIVE:To prepare Idebenone solid dispersion,and to investigate its dissolution rate in vitro. METHODS:Us-ing Poloxamer 407(P407)as carrier,the influence of preparation methods(solvent method,melting method)and the ratio of the drug to P407(1∶1,1∶3,1∶8)on the dissolution of drug were investigated by single factor design. The state of idebenone in ma-trix of solid dispersion was further determined by using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). RESULTS:Idebenone solid dispersion prepared by solvent method(the ratio of the drug to poloxamer was 1∶3)showed dissolution rate of 80%. The majority of idebenone existed in the solid dispersion at amorphous forms or molecular state. CONCLU-SIONS:Idebenone solid dispersions with high dissolution rate in vitro is prepared successfully.

Analysis on antimicrobial susceptibility of bacteria on Poloxamer 407 gel / 重庆医学

Objective To evaluate the antimicrobial susceptibility of bacteria cultured on a Poloxamer 407(P407) thermosensi-tive in-situ gel .Methods The modified Kirby Bauer(K-B) disc diffusion method was adopted to determine the drug susceptibility of 9 kinds of bacterium isolated on the P407 and the Mueller Hinton(MH)agar culture medium, at the same time the diffusion rates of different antibacterial drugs on the P407 and the MH agar culture medium were compared;the sodium dodecylsulfate polyacrylam-ide gel electrophoresis(SDS-PAGE) was adopted to analyze the outer membrane proteins (OMPs) expression of Pseudomonas aeruginosa on these two kinds of culture medium .Results In the antimicrobial susceptibility tests, the inhibition zones on the P407 gel were found to be generally smaller than those on the MH agar.The difference in the diffusion rates of the antibacterial drugs on these two kinds of culture medium had no statistically significant difference (P> 0.05);the OMPs expression of Pseudomonas aeruginosa was similar to its growth expression on the P407 culture medium ,but different from its expression on the MH agar .Con-clusion P407 as an excipient of bacteria culture medium can be used in the screening test of the biofilm antimicrobial susceptibility .

Determination and Stability of Nimesulide in Thermo-sensitive Hydrogels / 中国药师

Objective:To establish the method for determining nimesulide in thermo-sensitive hydrogels and study the stability of the preparation. Methods:An HPLC method was adopted with a Shim-Pack C18-ODS (150 mm × 4. 6 mm,5 μm) column, the mobile phase was composed of menthol-water-acetic acid (65∶35∶0. 8) with the flow rate of 1. 0 ml·min-1 at 30℃, the detection wavelength was at 299 nm, and the injection volume was 10 μl. Results:The separation of nimesulide, impurities and degradation products was good. The linear range of nimesulide was 2. 43-24. 37μg·ml-1(r=0. 999 8), the average recovery was 100. 02%(RSD=1. 12%, n=5). The lowest detectable limit and the lowest quantitation limit was 0. 098μg·ml-1 and 0. 25μg·ml-1, respectively. The stabil-ity results of hard-light exposure, destructive testing and long-term testing showed that the preparation was basically stable at room tem-perature, while under high temperature with hard light, strong basicity, acidicity or oxidation solution, the preparation was unstable. Conclusion:The method is accurate and reliable in the determination and stability study of nimesulide thermo-sensitive hydrogels. The hydrogels should be stored in shady, cool and dark place.

The Effect of Poloxamer 407-Based Hydrogel on the Osteoinductivity of Demineralized Bone Matrix

BACKGROUND: Demineralized bone matrix (DBM) is used for bone healing due to its osteoinductivity, but it requires a carrier for clinical application. Here, we report the effects on the osteoinductivity of DBM by use of a poloxamer 407-based hydrogel as the carrier, compared to sterile water. METHODS: DBM-W and DBM-H represent 27 wt% of DBM with sterile water and DBM with a poloxamer 407-based hydrogel, respectively. Both of the compositions were applied to human mesenchymal stem cell (MSC) cultures, and monitored for alkaline phosphatase (ALP) staining and ALP activity. Six 10-week-old athymic nude rats were used for abdominal muscle grafting with either DBM-W or DBM-H, and were tested by plane radiography, microfocus X-ray computed tomography (CT), and decalcified histology to evaluate ectopic bone formation. RESULTS: The DBM-W group showed stronger ALP staining at 7, 14, and 21 days of treatment, and significantly higher ALP activity at 7 and 14 days of treatment, compared to the DBM-H group. Plane radiography could not confirm the radio-opaque lesions in the rat ectopic bone formulation model. However, ectopic bone formation was observed in both groups by micro-CT. Compared to the DBM-H group, the DBM-W group showed higher bone volume, percent bone volume and trabecular number, and the difference in percent bone volume was statistically significant. Decalcified histology found bony tissue with lamellation in both groups. CONCLUSIONS: Our results suggest that poloxamer 407-based hydrogel has efficacy as a DBM carrier since it shows ectopic bone formation, but its effects on the quality and quantity of osteoblastic differentiation in rat abdominal ectopic bone and MSC are considered negative.

Study of Binary and Ternary Solid Dispersion of Spironolactone Prepared By Co-Precipitation Method for the Enhancement of Oral Bioavailability.

The study was designed to formulate novel spironolactone, a BCS class II drug loaded solid dispersion system (SDs) with improved dissolution rate. For this purpose binary and ternary solid dispersion were prepared by co-precipitation method using Poloxamer-407 only and mixture of poloxamer-407 with a second polymer such as HPMC 6cps, HPC, Kollicoat IR, Kollidon VA 64 respectively. To prepare binary SDs poloxamer 407 was used in three concentrations: 33%, 50% and 66.67% wt/wt of total SDs, whereas in case of ternary SDs, poloxamer 407 was used at 15%, 25% 35% wt/wt of the total SDs content and the concentration of the second polymer is maintained at fixed amount (1gm). In vitro dissolution study was carried out in a USP type II dissolution apparatus in 0.1 N hydrochloric acid solution for 1 hour. Release property of spironolactone from two different SDs was examined. Both the systems showed improved release profile compared with pure spironolactone powder. Enhanced release of spironolactone from the optimized SDs was characterized in light of cumulative percent release, % release after 5 min of dissolution and release rate of the drug from different SDs. When the amount of carriers increased with a decrease in drug content, the release of spironolactone was elevated. And it was found that almost two fold increase in the release of spironolactone while 66.67% poloxamer was used.

Formulation and evaluation of sustained release ondansetron poloxamer based solid suppositories.

The present investigation studies the effect of water swellable polymer hydroxylpropylmethyl cellulose (HPMC K4M, Methocel) on in vitro release of ondansetron from suppositories. Suppositories were prepared by using mixture of Poloxamer 407 and Poloxamer 188 hydrophilic bases. Suppositories containing 16 mg of ondansetron were prepared by fusion method. Weight variation, content uniformity, breaking (hardness), disintegration time, melting point and liquefaction time of the formulations were determined. In vitro release test was carried out according to USP XXII basket method. In vitro release data demonstrates ondansetron release from suppositories up to 12hrs and follows the zero order kinetics from poloxamer mixture based suppositories.

Preparation of bioadhesive cyclosporine a ocular nanostructured lipid carriers and its ocular distribution in rabbits / 中国药学杂志

OBJECTIVE: To develop a bioadhesive nanostructured lipid carrier (P407-NLC) for ocular delivery of cyclosporine A and investigate its ocular distribution in rabbits. METHODS: Melt-emulsification method was chosen to prepare CsA-NLC. Poloxamer 407 (P407) was dissolved in borate buffer solution (pH 8.0), then added into CsA-NLC to prepare P407-NLC. The morphology of P407-NLC was observed by transmission electron microscopy (TEM). The mean particle size and Zeta potential were measured by laser particle size analyzer. The viscosity was measured by rheometer. Dialysis method was employed to investigate the in vitro release of CsA from P407-NLC at 34°C. The concentrations of CsA in ocular tissues were studied by RP-HPLC, and the pharmacokinetic parameters were calculated by linear trapezoidal method. The topical ocular irritation study of P407-NLC was carried out in rabbits. RESULTS: The obtained P407-NLC was approximately spherical in shape with average particle size of (41.2 ± 0.2) nm and Zeta potential of (-15.2 ± 0.21) mV, and P407 was coated on the appearance of NLC. P407-NLC was non-newtonian fluids. The in vitro release of CsA from P407-NLC was slowed down and fitted well with single exponential distribution model. AUC0-24h of CsA in cornea, aqueous humor and iris after ocular administration of P407-NLC containing 6.0% P407 were 10.75, 4.45 and 4.62 times higher than that of CsA oil solution, and 2.77, 1.22 and 1.54 times higher than that of CsA-NLC, respectively. MRTs in aqueous humor, cornea and iris were 3.28, 2.26 and 3.46 times higher, respectively, than that of CsA oil solution, and 1.69, 1.50 and 1.62 times higher than CsA-NLC, respectively. There was no irritation for P407-NLC to rabbit eyes. CONCLUSION: P407-NLC can be used to increase the level of CsA in ocular tissues and would be a promising nanocarrier for ocular drug delivery. Copyright 2012 by the Chinese Pharmaceutical Association.

Study of binary and ternary solid dispersion of ibuprofen for the enhancement of oral bioavailability.

To develop a novel ibuprofen loaded solid dispersion system (SDs) with enhanced dissolution rate, binary and ternary solid dispersion were prepared by co-precipitation method using poloxamer-407 only and mixture of poloxamer-407 with a second polymer such as HPMC 6cps, HPC, Kollicoat IR, Kollidon VA 64 respectively. In case of binary SDs, poloxamer 407 was used in three concentrations: 33%, 50% and 66.67% wt/wt of total SDs. In case of ternary SDs, poloxamer 407 was used at 15%, 25% 35% wt/wt of the total SDs content while maintaining the concentration of the second polymer at fixed amount (1gm). In vitro dissolution study was conducted in phosphate buffer of pH 6.8 for 1h. Release property of ibuprofen from two different SDs was investigated. And in case of both the systems, enhanced release property was found where the release was compared with pure ibuprofen powder. Enhanced release of ibuprofen from the optimized SDs was characterized in light of cumulative percent release, % release after 5 min of dissolution and release rate of the drug from different SDs. When the amount of carriers increased with a decrease in drug content, the release of ibuprofen was elevated. And it was found that almost two fold increase in the release of ibuprofen while 66.67% poloxamer was used.

Formulation and evaluation of etoricoxib tablets employing cyclodextrin- poloxamer 407 - PVPK30 inclusion complexes.

Etoricoxib, a widely prescribed anti-inflammatory drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating etoricoxib – CD (βCD/ HPβCD) – Poloxamer 407 and etoricoxib – CD (βCD/ HPβCD) –PVP K30 inclusion complexes into tablets and to evaluate the effects of CDs, Poloxamer 407 and PVP K30 on the dissolution rate of etoricoxib tablets. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug – CD –Poloxamer 407 / PVP K30 inclusion complexes. Drug – CD- Poloxamer 407 / PVP K30 inclusion complexes were prepared by kneading method. Tablets each containing 60 mg of etoricoxib were prepared by wet granulation and direct compression methods employing various CD complexes and the tablets were evaluated for dissolution rate and other physical properties. toricoxib tablets made by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Tablets formulated employing βCD complexes disintegrated relatively more rapidly than those formulated employing HPβCD complexes. Etoricoxib dissolution was rapid and higher from the tablets formulated employing drug- CD- Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing etoricoxib alone and drug – CD complexes in both wet granulation and direct compression methods. In both the methods tablets formulated employing βCD complexes gave higher dissolution rates (K1) and DE30 values when compared to those formulated employing HPβCD complexes. Tablets formulated employing dug – βCD – Poloxamer 407 and drug – βCD – PVP K30 complexes and prepared by direct compression method gave higher dissolution rates, 0.0539 and 0.0459 min-1 respectively when compared to plain tablets (0.0124 min-1 ) as well as tablets containing drug – βCD complexes (0.0417 min-1). Hence a combination of βCD with Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate of etoricoxib tablets.

Anti-hyperlipidemic and antioxidant potential of different fractions of Terminalia arjuna Roxb. bark against PX- 407 induced hyperlipidemia.

The three fractions diethyl ether, ethyl acetate and ethanol. of T. arjuna exerted hypolipidemic and antioxidative effects at two different doses levels of 175 and 350 mg/kg body weight in Poloxamer (PX)-407 induced hyperlipidemic albino Wistar rats. The hypolipidemic and antioxidant effects of T. arjuna fractions were noticed as EtOH>diethyl ether>ethyl acetate. The results suggest that ethanolic fraction of T. arjuna possesses the potent properties of being antioxidant and hypolipidemic than other fractions. In turn, it has therapeutic potential for the prevention of coronary arterial disease.

Development, characterization and solubility study of solid dispersion of nifedipine hydrochloride by solvent evaporation method using poloxamer 407.

The present research endeavor was towards the enhancement of solubility of nifedipine by solid dispersion method, were prepared by solvent evaporation method and polymers Poloxamer 407 was tried with different proportion with drug and increasing the different sodium lauryl sulphate (SLS) percentages. There was significant increase of dissolution rate of nifedipine, in SD of nifedipine + Poloxamer 407 (1:4) than nifedipine + Poloxamer 407 (1:2) and nifedipine + Poloxamer 407 (1:3). Solid dispersion of nifedipine was evaluated by solubility test, DSC, IR and dissolution characteristics. Solid Dispersion of Nifedipine in Poloxamer 407 improved the dissolution rate of nifedipine, which helps to enhancing solubility of Nifedipine. Dissolution rate of pure nifedipine increased, with increasing the various Polymers content and with increasing the various sodium lauryl sulphates (SLS) content. The solubility of pure nifedipine was observed in pH 7.2 ± 0.2 buffer solution, with increasing the polymer ratio as 1:2, 1:3, 1:4 and with increasing the SLS percentage(%) as 1%, 3% and 5% respectively.