Surface Engineering of Fenofibrate Nanocrystals Using Nano-by-Design Multivariate Integration: A Biopharmaceutical and Pharmacokinetic Perspective

2021 ◽  
Vol 18 ◽  
Author(s):  
Sandip Gite ◽  
Pratik Kakade ◽  
Vandana Patravale
Keyword(s):  
Surface Engineering ◽  
In Vitro Release ◽  
Development Stage ◽  
Lipid Lowering ◽  
Onset Of Action ◽  
Factors Affecting ◽  
Stabilizer Concentration ◽  
Potential Risk Factors ◽  
Intrinsic Solubility

Introduction: Surface engineering of nanocrystals for improving the biopharmaceutical features is a multivariate process involving numerous formulation and process variables, thus making it a complicated process to get the desired biopharmaceutical quality profile. Nano-by-design is hereby proposed as an approach to nanonize an orally active, lipid lowering fenofibrate, to improve feasibility in product development. Methodology: Top-down wet ball milling (media milling) in zirconia planetary chamber was methodically explored for improving the solubility and bioavailability of fenofibrate by formulating a nanosuspension using polyvinyl alcohol as a stabilizer. Several influencing variables were screened using a systematic one-factor-at-a-time approach. DSC, SEM, XRD, and FTIR were utilized for physical characterization of the product during the development stage and study the effect of milling time, milling speed, fenofibrate: stabilizer ratio, premilling time and stabilizer concentration. Potential risk factors affecting critical quality biopharmaceutical attributes of fenofibrate nanocrystals like size, zeta potential, in vitro release, crystallinity and intrinsic solubility were optimized to improve pharmacokinetic performance. Result: Formulated nanosized fenofibrate exhibited a crystalize nature as evident from XRD and DSC, 411 nm size, and a rapid but complete dissolution (~99% in 30 min). This resulted into quick onset of action and improved bioavailability as observed from 51.46% shorter Tmax, 82.63% higher Cmax, and 69.34% higher AUC0–24h, respectively.

Factors Affecting the Acoustic In Vitro Release of Calcein from PEGylated Liposomes

2019 ◽  
Vol 19 (11) ◽  
pp. 6899-6906 ◽  
Author(s):  
Salma E. Ahmed ◽  
Hesham G. Moussa ◽  
Ana M. Martins ◽  
Yassmine Abbas ◽  
Mohammad H. Al-Sayah ◽  
...  
Keyword(s):  
In Vitro Release ◽  
Pulsed Ultrasound ◽  
Factors Affecting ◽  
Stealth Liposomes ◽  
Experimental Parameters ◽  
Drug Doses ◽  
Cancerous Cells ◽  
Vitro Release ◽  
Frequency Power

Typical methods used in cancer treatment, including chemotherapy, are debilitating because of the various adverse side effects experienced by cancer patients. The free drug injected into the patient at given doses affects both healthy and cancerous cells. Therefore, novel methods are being researched to ensure the selectivity of the treatment. The purpose of this study is to test the release of a model fluorescent drug, calcein, from echogenic stealth liposomes, triggered by lowfrequency pulsed ultrasound. Several experimental parameters related to the ultrasound (US) and the investigated liposomes were varied in order to examine their effect on the acoustic release. Upon analysis of experimental results, the study concluded that release can be maximized by optimizing the sonication frequency, power density, and US pulse duration. When a non-isothermal chamber is used to conduct the experiments, it is important to have longer ‘Off’ than ‘On’ US periods in order to avoid overheating the liposomes. Applying such pulsation pattern can also be utilized to achieve slower release rates, which safely meet the desired drug levels at the end of the session. Our study also concluded that optimizing the liposome concentration is vital to delivering desired drug doses. Additionally, the type of lipids used in the synthesis should be carefully selected to produce stable yet acoustically sensitive liposomes capable of releasing at desired rates.

scholarly journals Enhanced Dissolution of Sildenafil Citrate Using Solid Dispersion with Hydrophilic Polymers: Physicochemical Characterization and In Vivo Sexual Behavior Studies in Male Rats

Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3512
Author(s):  
Mohammed F. Aldawsari ◽  
Md. Khalid Anwer ◽  
Mohammed Muqtader Ahmed ◽  
Farhat Fatima ◽  
Gamal A. Soliman ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
In Vitro Release ◽  
Physicochemical Characterization ◽  
Hydrophilic Polymers ◽  
Sildenafil Citrate ◽  
Male Rats ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Onset Of Action

Sildenafil citrate (SLC) is a frequently used medication (Viagra®) for the treatment of erectile dysfunction (ED). Due to its poor solubility, SLC suffers from a delayed onset of action and poor bioavailability. Hence, the aim of the proposed work was to prepare and evaluate solid dispersions (SDs) with hydrophilic polymers (Kolliphor® P188, Kollidon® 30, and Kollidon®-VA64), in order to enhance the dissolution and efficacy of SLC. The SLC-SDs were prepared using a solvent evaporation method (at the ratio drug/polymer, 1:1, w/w) and characterized by Differential Scanning Calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscope (SEM), drug content, yield, and in vitro release studies. Based on this evaluation, SDs (SLC-KVA64) were optimized, with a maximum release of drug (99.74%) after 2 h for all the developed formulas. The SDs (SLC-KVA64) were further tested for sexual behavior activity in male rats, and significant enhancements in copulatory efficiency (81.6%) and inter-copulatory efficiency (44.9%) were noted in comparison to the pure SLC drug, when exposed to the optimized SLC-KVA64 formulae. Therefore, SD using Kollidon®-VA64 could be regarded as a potential strategy for improving the solubility, in vitro dissolution, and therapeutic efficacy of SLC.

scholarly journals Study of factors affecting the in vitro release of diclofenac sodium from hypromelose-based gels

2021 ◽  
pp. 12-31
Author(s):  
Elena Bezuglaya ◽  
Hanna Ivashchenko ◽  
Nikolay Lyapunov ◽  
Igor Zinchenko ◽  
Anna Liapunova ◽  
...  
Keyword(s):  
Apparent Viscosity ◽  
Flow Behavior ◽  
Diclofenac Sodium ◽  
In Vitro Release ◽  
Newtonian Liquid ◽  
Resonance Spectroscopy ◽  
Spin Probes ◽  
Factors Affecting ◽  
Vitro Release

The aim of our study was to identify factors affecting the in vitro release of diclofenac sodium (DS) from hypromellose-based gels (HPMC). Materials and methods. Gels with HPMC and liquids without HPMC were studied by viscosity-rotating viscometer method and spin probe electron paramagnetic resonance spectroscopy. Rheograms were used to determine the flow behavior and the apparent viscosity, and the EPR spectra were used to determine the rotational correlation time (τ–1) of the dissolved spin probes. The in vitro release tests were performed using vertical diffusion cells according to a validated procedure. The assay of DS and isopropyl alcohol (IPA) in the receptor medium was performed by high performance liquid chromatography (HPLC) and gas chromatography (GC) according to validated procedures, and the water content was determined using semi-micro method. Results. The apparent viscosity of the gels increased with increasing HPMC content and depended on the HPMC grade. The high apparent viscosity of the gels did not affect the values of τ–1 of the dissolved spin probes. In viscous gels and Newtonian fluids, the composition of which corresponded to the dispersion medium of gels, the values of τ–1 were identical and were in the range of rapid rotation, which is a prerequisite for similar and rapid release of the dissolved substances from gels and liquids. It was shown that the HPMC-based gel and Newtonian liquid without HPMC in terms of in vitro release parameters DS and IPA were equivalent. During in vitro testing the release of dissolved DS increased with increasing its concentration in the gel and depended on the dispersed state of DS. When the content of IPA was changed from 45.0 % to 22.5 %, the water absorption by the gel and the release of IPA decreased, and the release of DS increased, which was due to the decrease in the solubility of DS in the gel. Conclusions. HPMC, which provided high apparent viscosity of the gels, did not affect the value of τ–1 of the dissolved spin probes and the in vitro release of DS from the gels. The gel and Newtonian liquid were equivalent in terms of in vitro release of DS and IPA. The release of DS altered proportionally with the concentration of DS and depended on its dispersed state. As the content of IPA decreased, the release of IPA decreased, but the release of DS increased because of the decrease in the solubility of the DS in the gel

scholarly journals Formulation Development and Evaluation of Mouth Dissolving Tablets of Loratadine

1970 ◽  
Vol 2 (2) ◽  
pp. 59-65
Author(s):  
Abu Kalam Lutful Kabir ◽  
Shaikh Mukidur Rahman ◽  
Md Arshad Jahan ◽  
Abu Shara Shamsur Rouf
Keyword(s):  
Age Groups ◽  
In Vitro Release ◽  
Angle Of Repose ◽  
Formulation Development ◽  
Onset Of Action ◽  
Compression Technique ◽  
Disintegration Time ◽  
Wetting Time ◽  
Croscarmellose Sodium

Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly and pediatrics. Mouth dissolving tablets constitute an innovative dosage forms that overcome the problems of swallowing and provides a quick onset of action. The purpose of this study was to formulate and evaluate mouth dissolving tablet of loratadine using a special preparation technology (pharmaburst Technology) with a super disintegrating agent (Croscarmellose sodium). Tablets were prepared by direct compression technique. The granules were evaluated for angle of repose, bulk density, tapped density, bulkiness, compressibility index and hausners ratio. The tablets were evaluated for hardness, thickness, uniformity of weight, friability, wetting time, water absorption ratio, disintegration time and drug content. In vitro release studies were performed using USP-II (paddle method) in 900ml of pH 1.2 at 50rpm. The physical properties of the prepared tablets did not show any significant variations and were found to have good physical integrity. Tablets prepared with pharmaburst B2 and Croscarmellose sodium showed a lesser disintegration time and wetting time of 27±0.10 and 38±0.13 seconds respectively. The best formulations were subjected to stability studies at 40ºC/75% RH for 60 days. Key words: Loratadine; pharmaburst B2; croscarmellose sodium; mouth dissolving tablets; direct compression.DOI: 10.3329/sjps.v2i2.5825Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 59-65

scholarly journals Formulation and Evaluation of Tablets Containing Fenugreek Extract Using Sodium Starch Glycolate as Super Disintegrant

2021 ◽  
pp. 47-53
Author(s):  
Divya Jyothi
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Physicochemical Characterization ◽  
Antidiabetic Activity ◽  
Wet Granulation ◽  
Onset Of Action ◽  
Plant Materials ◽  
Sodium Starch Glycolate ◽  
Tablet Formulations

The present work is aimed to formulate the tablets containing fenugreek extract as drug by wet granulation method. Further the effect of Sodium Starch Glycolate as super disintegrant on disintegration and drug release was studied. Fenugreek extract contains mucilage which retards the disintegration of tablets and hence shows slower drug release. Hence in order to improve disintegration and thereby in vitro drug release, Sodium Starch Glycolate was used as super disintegrant. Tablet formulations were prepared without the SSG (Conventional-F1) and also with sodium starch glycolate (F2-F4) by wet granulation method. Assessment of flow properties of granules, physicochemical characterization of tablet formulations was carried out. Fenugreek is widely used for its antidiabetic activity which is attributed to mainly to the presence of an alkaloid Trigonelline. Hence in vitro release study of trigonelline was carried out which showed that the percentage release from F1 and F2 was found to be 58.12±4.49 and 99.08±0.01 respectively after 6 hrs. This study concludes that tablet formulation of fenugreek seed extracts with super disintegrants will be more desirable, advantageous and therapeutically more beneficial than incorporating the direct plant materials for the treatment of diabetes for faster onset of action.

scholarly journals Formulation and Evaluation of Curcumin Loaded Nanoliposome on Brain Targeted

2021 ◽  
Vol 11 (1) ◽  
pp. 31-43
Author(s):  
Jyoti Kumari ◽  
◽  
Lovely Chaurasia ◽  
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Brain Targeting ◽  
Dispersion Method ◽  
Active Constituent ◽  
Factors Affecting ◽  
Ir Studies ◽  
Transmission Electron ◽  
The Central Nervous System

The present work aimed to produce Curcumin based nanoliposomes that nanoliposome can target the site via the brain in a controlled manner. Nanoliposomes are important in controlling the carriage; Curcumin which is an active constituent of curcuminoids thus also provides an effective treatment for the central nervous system and plays a crucial role. The interaction of the drug was ruled out by FT-IR studies and no incompatibility and lipids and surfactant. To optimize the formulation, factors affecting the physical appearance of Nanoliposomes were investigated. Curcumin-loaded Nanoliposomes were formulated using cholesterol by physical dispersion method and characterized for particle size, drug content, stability, production yield. Prepared nanoliposomes gave the better physical, morphological concerning the concentration of the lipids, surfactant, and ratio of lipid and surfactant. Six different formulations of Nanoliposomes F1-F6 were formulated to obtain the optimized formulation. The TEM (Transmission Electron Microscopy) of Nanoliposomes showed that they were rounded in shape and porous in texture. In-vitro drug release of formulation indicates that formulation F6 was selected as an optimized formulation for incorporation into the nanoliposomes among all the six formulations and liposome showed drug release in a controlled manner at the end of 10 hours. Keywords: Curcumin, Nanoliposomes, Physical Dispersion Method, Brain Targeting, Blood-Brain Barrier, Cholesterol, Bioavailability, In vitro Release.

scholarly journals Enhancement of Aqueous Solubility and Dissolution Profile of Atorvastatin Calcium: In vitro Evaluation of Solid Dispersion

2021 ◽  
pp. 1-7
Author(s):  
Pawar AR ◽  
◽  
Mehetre JS ◽  
Keyword(s):  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Lipid Lowering ◽  
Dissolution Profile ◽  
High Permeability ◽  
Onset Of Action ◽  
Atorvastatin Calcium ◽  
Lipid Lowering Agent ◽  
Low Solubility

Purpose: The objective of the present study was to formulate solid dispersions (SD) of Atorvastatin calcium to improve the aqueous solubility and dissolution rate to facilitate faster onset of action. Atorvastatin calcium is a lipid lowering agent belonging to BCS-II having low solubility and high permeability.

Comparative Evaluation of Isoniazid and Rifampicin Dispersible Tablets Prepared by Direct Compression and Sublimation Methods

2013 ◽  
Vol 6 (4) ◽  
pp. 2225-2239
Author(s):  
Uday Bolmal ◽  
C K Pandey ◽  
V Phatarpekar ◽  
N G Dhople ◽  
Rajkumar Kotha
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Simultaneous Estimation ◽  
Direct Compression ◽  
Drug Release Profile ◽  
Onset Of Action ◽  
Sublimation Method ◽  
Dispersible Tablets ◽  
Release Data

Dispersible tablets are gaining popularity over conventional tablets due to its increased popularity for administration to pediatric and geriatric patients as it provides quick onset of action and ease of administration. An attempt had been made, to develop dispersible tablet of isoniazid and rifampicin combination by direct compression and sublimation method, to increase the bioavailability of the anti-tubercular agents as well to provide the local delivery in the case of oral tuberculosis. Formulation F1 to F8 (2% and 4% w/w of different superdisintegrants (crospovidone, pregelatinized starch, croscarmellose sodium and sodium starch glycolate) formulated by direct compression method. The formulations containing 4% of superdisintegrants (F2, F4, F6, and F8) were selected as optimized and hence 4% of superdisintegrants were used for sublimation method (F9 to F12). The effects of sublimating material (camphor) on drug release profile and disintegration property were evaluated. Studies on two different methods showed sublimation method as a better alternative as its formulations rapidly disintegrates, disperse and shows faster drug release (in 14 min) in comparison to direct compression (in 20 min). Pre-compression parameters of formulation blends indicated good flow properties and compressibility. Simultaneous estimation was performed for calculation of drug content and % drug release. In vitro release data analysis revealed 90% drug release. F9 formulation (sublimation) showed best anti-tubercular activity. F2, F9 formulations were found to be stable even after 90 days. Hence it is evident from this study that fast dissolving tablets could be a promising delivery system for isoniazid and rifampicin with improved drug availability and better patient compliance.

Sign in / Sign up

Export Citation Format

Share Document