NANOPRECIPITATION TECHNIQUE FOR PREPARATION OF STERICALLY STABILIZED RISPERIDONE NANOSUSPENSION: IN VITRO AND IN VIVO STUDY

Objective: Risperidone is an atypical antipsychotic drug used to treat schizophrenia; however it suffers from a poor aqueous solubility, which delays its onset of action. Therefore, the purpose of the present study is to utilize the nanotechnology to formulate nanoparticles that enhance the dissolution and hence the bioavailability of risperidone.Methods: Nanosuspensions were prepared by nano precipitation method in the presence of selected stabilizers at different concentrations. The nanosuspensions were evaluated for their particle size, zeta potential, drug content and In vitro drug dissolution. The selected formula was freeze dried and characterized by scanning electron microscopy (SEM), fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffractometry studies (XRD) and pharmacokinetic study.Results: The in vitro dissolution showed higher drug release compared to the pure drug. The optimum formula has an average particle size of 215.56±12.65 nm and zeta potential of-19.84±2.55mV. The bioavailability parameters in the rabbits were enhanced by 2 folds when compared with the marketed tablets (Risperidal®).Conclusion: Nanoprecipitation method was successfully employed to produce stable risperidone nanosuspension by using the proper stabilizer (pluronic F 127). Risperidone nanoparticles may be a promising formula that improves the dissolution and hence oral bioavailability of poorly water soluble risperidone. Keywords: Risperidone, Nanosuspension, Pluronic F127, Nanoprecipitation, Bioavailabilit

FORMULATION AND OPTIMIZATION OF SOLID SELF-NANOEMULSIFYING SYSTEM USING POROUS CARRIERS FOR ORAL DELIVERY OF CINNARIZINE

Objective: The present study aims to utilize the nanotechnology technique to formulate the Cinnarizine (CNZ) in the form of solid self-nano emulsifying system to enhance the dissolution and hence the bioavailability.Methods: Screening study for solubility of CNZ in different vehicles was carried out. The selected system was optimized for saturated solubility, globule size, zeta potential, polydispersity index (PDI) and self-emulsification time. The solidified nanoemulsion was prepared using; Aeroperl 300, Aerosil 200, hydrophilic nanosilica and Neusilin US2 as porous carrier materials. The compressed CNZ tablets were evaluated regarding their physicochemical characteristics, in-vitro release, and bioavailability study.Results: Self nano-emulsifying system composed of Labrafil (oil), tween 80 (surfactant), and transcutol (cosurfactant) was successfully developed with a droplet size range of 11.37-92.58 nm. The in-vitro release results revealed that the developed formulation improved the release of CNZ and enhanced the bioavailability in the rabbits (190%) more than the commercial product (Stugeron® tablets).Conclusion: Solid self-nano-emulsifying system of CNZ was successfully developed by different ratios of Labrafil (oil), tween 80 (surfactant), transcutol (cosurfactant) and solidified by the adsorption on hydrophilic nano silica and the optimized formula could be expected to increase and improve the bioavailability of CNZ.Â

EFFECT OF BIODEGRADABLE CO-POLYMERS AND DIVALENT CATIONS ON THE SUSTAINED RELEASE ABILITY OF PROPRANOLOL HYDROCHLORIDE LOADED BIOMATERIAL MICROSPHERES

Objective: Propranolol Hydrochloride (PHCL) is used for the treatment of hypertension and angina pectoris; however it has two major problems; short biological halfâ€life and low bioavailability, so the aim of the present work was to develop PHCL mucoadhesive microsphere to prolong the residence time at the absorption site, therefore, increase the bioavailability.Methods: PHCL microspheres were prepared by ionotropic gelation method using nature polymers. Factorial design (33) was used to develop PHCL mucoadhesive microspheres, the independent factors used were polymer type (Sodium carboxymethyl cellulose (Na CMC), and Hydroxyl propyl methyl cellulose (HPMC), Carpobol 940), cross-linking type (calcium chloride, zinc chloride and barium chloride) and the concentration of Chitosan (0.5, 1, 1.5 %w/v). The developed microspheres were physicochemical characterized. The selected formula was selected for mucoadhesive test and in vivo study on human volunteers.Results: The results revealed that the PHCL mucoadhesive microspheres have good flowability, the mean particle sizes ranged from 541 to 815 µm and the entrapment efficiency ranged from 35.6% to 69.53%. The selected PHCL microspheres showed spherical particles with a rough surface and exhibited a slow release over 8h. The pharmacokinetic data of selected PHCL microspheres showed prolonged Tmax, decreased Cmax and AUC0–∞ value of 926.21±40.74ng. h/ml indicating improved relative bioavailability by144.93% compared with marketed tablets.Conclusion: PHCL microspheres were successfully prepared by ionic gelatin method that retards the release and enhances the oral bioavailability.Keywords: Propranolol HCL, Microspheres, Ionic gelation method, Chitosan, Relative bioavailabilit

Comparative Pharmacokinetic Study of Two Lyophilized Orally Disintegrating Tablets Formulations of Vinpocetine in Human Volunteers

Vinpocetine is a poorly water soluble drug, commonly used in treatment of various cerebral insufficiency conditions. The aim of this work was to formulate vinpocetine in the form of orally disintegrating tablets (ODTs) and enhance its solubility and dissolution rate. This objective was addressed using lyophilization technique of either solid dispersion using polyethylene glycol 4000 (PEG 4000) or inclusion complex with 2-hydroxypropyl β-cyclodextrin (2HP-β-CD). Differential scanning calorimetry (DSC) and fourier transform-infrared (FT-IR) spectroscopy were used to characterize the solid state of the prepared solid complex. Tablets were prepared by direct compression using 23 factorial design to evaluate the effect of formulation variables (Ac-di-sol concentration 5 or 10%, the ratio of soluble polymer 1:1 or 1:3 and binder type 6% w/w Avicel PH102 or 6% w/w carboxymethyl cellulose) on release characteristics. Results showed that lyophilized ODTs disintegrated within few seconds and had significantly faster dissolution rate (70-100 % in 5 minutes) compared to the commercial oral tablet (Cavinton®). This was achieved at high content of PEG 4000 or 2 HP-β-CD in presence of 10 % w/w Ac-Di-Sol and 6 % w/w Avicel PH102. The extent of per oral absorption of vinpocetine was determined in healthy human volunteers using randomized crossover design. The relative bioavailability of selected solid dispersion and inclusion complex formulations were found to be 171.98 % and 196.06 % respectively. The study indicated that complexation of vinpocetine with 2-HP-βCD or dispersion in PEG 4000 followed by lyophilization are two successful strategies for enhancing the bioavailability of the drug from ODTs

Desarrollo y caracterización de una nueva formulación nano-lipoosómica de alendronato sódico con un polímero biodegradable

This work was supported by the pharmacological departmental grant.Background: Alendronate Sodium (ALDS) is the drug of choice for treatment of osteoporosis. However, 50% of the osteoporotic patients ceased the treatment within the first year due to its potential side effect on the gastrointestinal tract (GIT). Objective: The current study aimed to utilize nanotechnology to develop a nano-oral liposomal preparation containing biodegradable polymer (Starch) that enhance the drug prosperities. Methods: Nanoliposomes of ALDS were prepared using different concentrations of solubilized starch (0.1 - 0.5 g ) by thin film hydration method. A new method of alendronate quantitative determination was used to overcome the obstacle of its determination by using a new highly sensitive derivatization method. The selected formula was visualized using TEM, in vitro release studies and Stability study was also carried out. Furthermore, ulcerogenicity studies were performed to compare between the optimum prepared formula and a standard nonliposomal ALDS. Results: Six nano-oral liposomal formulations were prepared with zeta potentials ranging from -12 mV to -39 mV and a particle size ranging from 94 nm to 298 nm. The encapsulation efficiency studies demonstrated that the amount of ALDS entrapped within liposomes increased with increasing starch concentration. The stability studies confirmed the role of starch in increasing the stability of the prepared liposomes. In vitro release studies have demonstrated a relative delay in ALDS releases from the liposome core. Ulcerogenicity studies proofed that the prepared formula has a significant gastric tolerance. Conclusion: a novel liposomal formula of ALDS was developed with better tolerability. However, further clinical investigations are necessary to evaluate its therapeutic effectiveness.Antecedentes: El alendronato sódico (ALDS) es el fármaco de elección para el tratamiento de la osteoporosis. Sin embargo, el 50% de los pacientes osteoporóticos cesaron el tratamiento en el primer año debido a su posible efecto secundario en el tracto gastrointestinal (GIT). Objetivo: El presente estudio tiene como objetivo utilizar la nanotecnología para desarrollar una preparación liposomal nano-oral que contiene polímero biodegradable (almidón) que mejoran la prosperidad de la droga. Métodos: Se prepararon nanoliposomas de ALDS utilizando diferentes concentraciones de almidón solubilizado (0,1 - 0,5 g) mediante un método de hidratación de película delgada. Se utilizó un nuevo método de determinación cuantitativa de alendronato para superar el obstáculo de su determinación utilizando un nuevo método de derivatización altamente sensible. La fórmula seleccionada se visualizó utilizando TEM, estudios de liberación in vitro y se realizó también un estudio de estabilidad. Además, los estudios de ulcerogenicidad se realizaron para comparar entre la fórmula óptima preparada y un estándar no liposomal ALDS. Resultados : Se prepararon seis formulaciones liposomales nano-orales con potenciales zeta que oscilaban entre -12 mV y -39 mV y un tamaño de partícula que variaba de 94 nm a 298 nm. Los estudios de eficacia de la encapsulación demostraron que la cantidad de ALDS atrapada dentro de los liposomas aumentaba con el aumento de la concentración de almidón. Los estudios de estabilidad confirmaron el papel del almidón en el aumento de la estabilidad de los liposomas preparados. Los estudios de liberación in vitro han demostrado un retraso relativo en las liberaciones de ALDS del núcleo de liposomas. Los estudios de ulcerogenicidad demostraron que la fórmula preparada tiene una tolerancia gástrica significativa. Conclusión: se desarrolló una nueva fórmula liposomal de ALDS con mejor tolerabilidad. Sin embargo, otras investigaciones clínicas son necesarias para evaluar su efectividad terapéutica

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation.

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity

Fabrication and Appraisal of Simvastatin via Tailored Niosomal Nanovesicles for Transdermal Delivery Enhancement: In Vitro and In Vivo Assessment

Simvastatin (SIM) is a HMG-CoA reductase inhibitor employed in the management of hyperlipidemia. However, its low bioavailability limits its clinical efficacy. The objective of this study was to overcome the poor bioavailability of SIM via the transdermal application of a SIM-loaded niosomal gel. Niosomes loaded with SIM were fabricated by means of the thin-film hydration method and optimized through a 33-factorial design utilizing Design Expert® software. The prepared niosomes were evaluated for entrapment efficiency (EE%), zeta potential, vesicle size, and cumulative percentage of drug release. The optimum niosomal formulation was loaded on the gel and evaluated for physical properties such as color, clarity, and homogeneity. It was also evaluated for spreadability, and the cumulative % drug release. The best niosomal gel formula was appraised for ex vivo permeation as well as pharmacokinetic study. The SIM-loaded niosomes showed EE% between 66.7–91.4%, vesicle size between 191.1–521.6 nm, and zeta potential ranged between −0.81–+35.6 mv. The cumulative percentage of drug released was ranged from 55% to 94% over 12 h. SIM-loaded niosomal gels were clear, homogenous, spreadable, and the pH values were within the range of physiological skin pH. Furthermore, about 73.5% of SIM was released within 24 h, whereas 409.5 µg/cm2 of SIM passed through the skin over 24 h in the ex vivo permeation study. The pharmacokinetic study revealed higher AUC0–∞ and Cmax with topical application of SIM-loaded niosomal gel compared to topical SIM gel or oral SIM suspension. The topical application of SIM-loaded niosomal gel ascertained the potential percutaneous delivery of SIM