Development of Sublingual tablets of Bisoprolol Hemifumarate / Hydroxypropyl -β-Cyclodextrin Complex for Potential treatment of Angina Pectoris

Fast-disintegrating tablet drug delivery is gaining an importance for drug delivery technology especially for geriatric and pediatric patient because of swallowing difficulties.   In certain diseases such as hypertension and angina pectoris therapy, taking a fast pharmacological response is of important criteria. Thus, the aim of the present work was to prepare a novel fast disintegrating Bisoprolol Hemifumarate (BH) tablet formulation for sublingual administration based on the use of 2-hydroxypropyl-βcyclodextrin (HP-βCD) which forms an inclusion complex with (BH) to improve the permeability of the drug to sublingual membrane, in addition to mask the taste of the drug through the inclusion complex.  Attempt has been made to prepare fast disintegrating tablets of (BH) using superdistintegrants like crosscarmellose sodium and crospovidone in concentration of (5%). Eight different formulae (B1-B8) with variation in tablet excipients were prepared by direct compression method using different mucoadhesive polymers such as chitosan and polyethylene glycol 6000 at different concentration (3% and 6%) for reduction the flushing action of saliva and to provide enough contact time for drug to be absorbed. The tablets were evaluated for the weight variation, hardness, friability, wetting time, disintegration time and dissolution study. The formulae B2 and B7 possessed the lowest disintegration time due to the presence of the high concentration of chitosan, which has some disintegration action, thus were subjected to a pharmacokinetic study using human volunteers. The bioavailability of B2 was significantly higher than that of the reference (Concor®) (p > 0.05).  Thus, the present investigations suggest that (BH) sublingual tablets allowed the rapid tablet disintegration, improved bioavailability and effective in emergency treatment of anginal pain and hypertension

Development of Sublingual tablets of Bisoprolol Hemifumarate / Hydroxypropyl -β-Cyclodextrin Complex for Potential treatment of Angina Pectoris

Fast-disintegrating tablet drug delivery is gaining an importance for drug delivery technology especially for geriatric and pediatric patient because of swallowing difficulties.   In certain diseases such as hypertension and angina pectoris therapy, taking a fast pharmacological response is of important criteria. Thus, the aim of the present work was to prepare a novel fast disintegrating Bisoprolol Hemifumarate (BH) tablet formulation for sublingual administration based on the use of 2-hydroxypropyl-βcyclodextrin (HP-βCD) which forms an inclusion complex with (BH) to improve the permeability of the drug to sublingual membrane, in addition to mask the taste of the drug through the inclusion complex.  Attempt has been made to prepare fast disintegrating tablets of (BH) using superdistintegrants like crosscarmellose sodium and crospovidone in concentration of (5%). Eight different formulae (B1-B8) with variation in tablet excipients were prepared by direct compression method using different mucoadhesive polymers such as chitosan and polyethylene glycol 6000 at different concentration (3% and 6%) for reduction the flushing action of saliva and to provide enough contact time for drug to be absorbed. The tablets were evaluated for the weight variation, hardness, friability, wetting time, disintegration time and dissolution study. The formulae B2 and B7 possessed the lowest disintegration time due to the presence of the high concentration of chitosan, which has some disintegration action, thus were subjected to a pharmacokinetic study using human volunteers. The bioavailability of B2 was significantly higher than that of the reference (Concor®) (p > 0.05).  Thus, the present investigations suggest that (BH) sublingual tablets allowed the rapid tablet disintegration, improved bioavailability and effective in emergency treatment of anginal pain and hypertension

Formulation and Evaluation of Ketotifen Fumarate Fast Disintegrating Sublingual Tablets

The aim of this study was to formulate KF fast disintegrating sublingual tablets (FDSLTs).  KF has an oral bioavailability of only 50%, as it undergoes first pass metabolism in liver. Sublingual dosage form bypasses the metabolism of KF in liver and offers a fast relieve of asthma also it is not swallowed thus; improve the patient compliance especially for geriatric and pediatric patients, because of swallowing difficulties. To achieve this goal, superdisintegrants and diluents were evaluated for their effect on the disintegration behavior of KF fast disintegrating sublingual tablets. In addition, of enhancing the permeability and bioavailability of selected formulae through comlexation with 2-HP-β-CD.   A 24 full factorial design was applied for a screening study in which four factors were used at two levels.  Two of these factors, were the type of disintegrants; Ac-di-sol or Explotab, and the concentration of each disintegrant (3% or 5%w/w).  10%w/w Avicel PH101 or PEG6000 was used as binder and the filler was either spray dried lactose or granular mannitol. The weight variation, content uniformity, friability, hardness, disintegration time, and in-vitro dissolution of the prepared formulae were evaluated.  The formula F9 containing 5%w/w Ac-di-sol with 10%w/wAvicel PH101and granular mannitol as diluent which has the least disintegration time (about 20 seconds) and the highest dissolution rate was selected as best formula for bioequivalence study.  The mean plasma concentration–time courses for KF following the administration of FDSLTs  F9 (contains KF without compelxation with 2HP-βCD), Fc9 (contains KF/2HP-βCD complex) and Zaditen® (Novartis-Egypt) tablets  in six healthy male volunteers were found to be different following the three treatments, expressed with  higher Cmax by about 60% and 90% for both FDSLTs of F9 and Fc9 respectively,  and earlier tmax (by 1 h) values for  both of  FDSLTs F9 and Fc9 compared with Zaditen tablets. The relative bioavailability of Fc9 was 152.45% compared to 130.304% for F9 when Zaditen® tablets were taken as reference standard. The results indicate that KF/2-HP-βCD fast disintegrating sublingual tablets may serve as a successful strategy for enhancing the bioavailability of KF

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