Self-nanoemulsifying Drug Delivery Systems of Valsartan: Preparation and In-Vitro Characterization

The main objective this study is to prepare and evaluate the selfnanoemulsifying drug delivery (SNEDDS) system in order to achieve a better dissolution rate of a poorly water soluble drug valsartan.  The present research work describes a SNEDDS of valsartan using labrasol, Tween 20 and Polyethylene glycol (PEG) 400. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to check for the emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (labrasol ) with surfactant (tween20), co-surfactant (PEG 400) were found to be optimum formulations. Prepared formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self emulsication time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations  are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The prepared formulation has a significant improvement in terms of the drug solubility as compared with marketed tablet and pure drug, thus, this greater dissolution of valsartan from formulations could lead to higher absorption and higher oral bioavailability

Spray Drying as an Approach for Enhancement of Dissolution and Bioavailability of Raloxifene Hydrochloride.

The present study investigated the effect of spray drying raloxifene HCl (RHCL) with different classes of hydrophilic carriers (different grades of polyvinyl pyrrolidones) and cellulosic polymers) in order to determine the potential effect on dissolution rate and bioavailability of RHCL. Pre-formulation studies were conducted to select the appropriate carriers and drug:carrier ratio for preparing the spray dried compositions.The solid state interactions of the spray dried mixtures were evaluated by DSC & XRD. Preformulation studies revealed that amorphous compositions of RHCL could be obtained only with Plasdones (K12, K29/32 and S630). DSC studies showed that the crystalline nature of RHCL was significantly reduced on spray drying. Significant enhancement in dissolution rate was observed with the prepared spray dried compositions and out of the three grades of Plasdone, Plasdone K12 demonstrated the maximum enhancement in rate of release of RHCL. The pharmacokinetics of spray dried composition (1:1 RHCL: K12) and pure RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague Dawley rats. The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with spray dried mixture of RHCL, K12 (1:1) compared to animals treated with RHCL. Spray drying of RHCL with Plasdones, especially Plasdone K12, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability

Self-nanoemulsifying Drug Delivery Systems of Valsartan: Preparation and In-Vitro Characterization

The main objective this study is to prepare and evaluate the selfnanoemulsifying drug delivery (SNEDDS) system in order to achieve a better dissolution rate of a poorly water soluble drug valsartan.  The present research work describes a SNEDDS of valsartan using labrasol, Tween 20 and Polyethylene glycol (PEG) 400. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to check for the emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (labrasol ) with surfactant (tween20), co-surfactant (PEG 400) were found to be optimum formulations. Prepared formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self emulsication time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations  are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The prepared formulation has a significant improvement in terms of the drug solubility as compared with marketed tablet and pure drug, thus, this greater dissolution of valsartan from formulations could lead to higher absorption and higher oral bioavailability

Comprimidos de liberación inmediata de Valsartán y Efavirenz: El papel de la concentración de superdisgregantes

The objective of this study was to formulate directly compressible fast disintegrating tablets of poorly water solubledrugs with different extent of drug solubilities, like valsartan and efavirenz, as model drugs. Effect of varying concentrationsof different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate ondisintegration time and in vitro drug dissolution was studied. The disintegration time of the best immediate release tabletformulation among those tested was observed to be 21.5±1.26 sec and 20.16±0.85 sec for valsartan and efavirenz tabletscontaining 20% of Crospovidone, respectively. Drug release (from both valsartan and Efavirenz tablets) was faster fromformulations containing crospovidone compared to the other formulation. The effect was more apparent in Efavirenz,which has lesser aqueous solubility than valsartan. It was observed that 20% crospovidone was required to achieve80% drug release from efavirenz tablets. Differential scanning calorimetric studies did not indicate any drug-excipientincompatibility. In conclusion, directly compressible fast disintegrating tablets of valsartan and efavirenz with shorterdisintegration times and high dissolution rate were obtained and crospovidone seemed to be a better disintegrant forboth valsartan and efavirenz, based on disintegration time and T80% values obtained.El objetivo de este estudio fue formular comprimidos de rápida disgregación, obtenidos mediante compresión directa,de fármacos con baja solubilidad en agua y diferentes grados de solubilidad, tomando como modelo Valsartány Efavirenz. Se estudió el efecto de diversas concentraciones de diferentes superdisgregantes como crospovidona,croscarmelosa sódica y glicolato sódico de almidón sobre el tiempo de disgregación y la disolución del fármaco invitro. Se observó que el tiempo de disgregación del comprimido con mejor liberación inmediata, de entre todaslas formulaciones probadas, fue de 21,5 ± 1,26 s y 20,16 ± 0,85 s para los comprimidos de Valsartán y Efavirenz,respectivamente que contenían, en ambos casos, un 20% de crospovidona. La liberación del fármaco (tanto en loscomprimidos de Valsartán como Efavirenz) fue más rápida en el caso de las formulaciones con crospovidona encomparación con la otra formulación. El efecto fue más evidente en el caso de Efavirenz, cuya solubilidad en aguaes menor que la de Valsartán. Se observó que era necesario un 20% de crospovidona para obtener una liberacióndel fármaco del 80% en comprimidos de Efavirenz. Los estudios por calorimetría diferencial de barrido no indicaronninguna incompatibilidad fármaco-excipiente. En conclusión, se obtuvieron por compresión directa comprimidosde rápida disgregación de Valsartán y Efavirenz con tiempos de disgregación más cortos y una alta velocidad dedisolución. Además, la crospovidona resultó ser un mejor disgregante tanto para Valsartán como para Efavirenz,de acuerdo con el tiempo de disgregación y los valores T80% obtenidos

Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

Paruvathanahalli Siddalingam Rajinikanth,1,2 Jestin Chellian2 1School of Pharmacy, Taylors University, 2School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia Abstract: The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol® ATO 5 (glyceryl palmitostearate) and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 µg/cm2/h) as compared with plain 5-FU gel (2.85±1.12 µg/cm2/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 µg/cm2) as compared with that from the 5-FU plain gel (12.23±3.86 µg/cm2) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations. Keywords: nanostructured lipid carrier, topical delivery, controlled release, 5-fluorouracil, skin penetration, skin infectio

Personalized treatment approach for HER2-positive metastatic breast cancer.

Breast cancer (BC) is a leading global concern for women, with 30% being HER2-positive cases linked to poorer outcomes. Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Although these therapies have improved MBC management and patient outcomes, resistance can develop, reducing effectiveness. Personalized strategies based on tumor characteristics offer hope for better responses and longer outcomes. This review outlines insights into MBC patients responding well to anti-HER2 treatments, even across multiple treatment regimen. Recent immunotherapy, locoregional therapy, and liquid biopsy breakthroughs are covered, suggesting ways to increase long-term responders. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics

Stomach-Specific Controlled Release Gellan Beads of Acid-Soluble Drug Prepared by Ionotropic Gelation Method

The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 32 factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment