Development and Characterization of Olanzapine Loaded Poly(lactide-co-glycolide) Microspheres for Depot Injection: In vitro and In vivo Release Profiles

2019 ◽  
Vol 16 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Fahad Pervaiz ◽  
Mahmood Ahmad ◽  
Lihong Li ◽  
Ghulam Murtaza
Keyword(s):  
Bulk Density ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Infrared Spectrometry ◽  
Burst Release ◽  
In Vivo Release ◽  
Depot Injection ◽  
Vitro Release

Purpose: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. Methods: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. Results: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 μm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. Conclusion: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.

In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

2002 ◽  
Vol 81 (1-2) ◽  
pp. 145-154 ◽  
Author(s):  
Dorrit Bjerg Larsen ◽  
Stig Joergensen ◽  
Niels Vidiendal Olsen ◽  
Steen Honoré Hansen ◽  
Claus Larsen
Keyword(s):  
In Vitro Release ◽  
In Vivo Release ◽  
Vitro Release ◽  
Oily Solution

Comparative Effects of Opiate Agonists Methadone, Levorphanol, and Their Isomers on the Release of Cortical ACh in Vivo and in Vitro

1975 ◽  
Vol 53 (4) ◽  
pp. 540-548 ◽  
Author(s):  
K. Jhamandas ◽  
V. Hron ◽  
M. Sutak
Keyword(s):  
In Vitro Release ◽  
Spontaneous Release ◽  
In Vivo Release ◽  
Small Doses ◽  
Vitro Release ◽  
Cortical Slices

The effect of analgesically active opiate agonists dl-methadone, levorphanol, and their less active forms d-methadone and dextrorphan, respectively, were tested on, (a) the spontaneous release of cortical acetylcholine (ACh) in vivo; (b) the spontaneous and K+-evoked release of cortical ACh in vitro. The injections of dl-methadone, but not d-methadone, inhibited the output of ACh in vivo. Naloxone completely reversed this effect of methadone. Levorphanol in small doses inhibited, and in larger doses stimulated, the in vivo release of ACh. Both effects were antagonized by naloxone. Its dextroisomer dextrorphan was completely inactive. The in vitro release of ACh from cortical slices was inhibited by all four agents. The effects of analgesically active opiates dl-methadone and levorphanol on the in vitro release were not clearly separable from the effects of their inactive forms d-methadone and dextrorphan.

scholarly journals FORMULATION DEVELOPMENT OF COLON TARGETED MESALAMINE PELLETS: IN VITRO-IN VIVO RELEASE STUDY

2019 ◽  
pp. 125-132 ◽  
Author(s):  
JAGAN BAHEKAR ◽  
SHAILESH WADHER
Keyword(s):  
In Vitro Release ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Aminosalicylic Acid ◽  
Formulation Development ◽  
In Vivo Release ◽  
Release Study ◽  
Vitro Release

Objective: This study was intended to investigate the potential of the colon specificity approach comprising of use of pH-sensitive and time-dependent polymers in combination for precise colonic release of Mesalamine or 5-Aminosalicylic acid (5-ASA). Methods: The extrusion and spheronization method, preferably employed in industry for allowing high dose capacity to formulate, was used to prepare drug pellets. The Wurster coating technique used for aqueous coatings of Eudragit NE 40D as an inner coat and Eudragit FS30D as outer coat. The changing pH media used for in vitro release study of optimization batches for both the coating levels. A scanning electron microscope (SEM) was used to evaluate coating thickness and surface morphology. Results: The pharmacokinetic parameters of formulation evaluated by in vivo study in rabbits revealed that the uncoated formulation released the drug too early in the gastrointestinal tract (GIT) with a mean Cmax of 1205.28±0.37 µg/ml at 2 h after administration, whereas desired lag time was achieved in case of coated pellets exhibiting mean Cmax 465.94±0.21 µg/ml and tmax of 8 h. Conclusion: The in vitro and in vivo release study divulge the reliability of approach involving the use of pH sensitivity and time dependency of polymer for drug release in a single formulation for the treatment of colonic diseases. Hence, the present study provides constructive results for colon targeting of 5-ASA pellets with industrially feasible processes.

scholarly journals Preparation and in vitro release of fluorouracil polylactide glycolide-polyethylene glycol monomethyl ether nanoparticles

2019 ◽  
Author(s):  
Anil Shumroni ◽  
David Gupta
Keyword(s):  
Polyethylene Glycol ◽  
Encapsulation Efficiency ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Monomethyl Ether ◽  
Burst Release ◽  
Average Particle ◽  
Glycol Monomethyl Ether ◽  
Vitro Release

AbstractThis report demonstrates a novel strategy to prepare fluorouracil polylactide glycolide-polyethylene glycol monomethyl ether (PLGA-mPEG) nanoparticles and study their in vitro release characteristics. Fluorouracil PLGA-mPEG nanoparticles were prepared by nanoprecipitation method. The encapsulation efficiency was determined by high performance liquid chromatography. Based on the single factor experiment, the prescription and preparation process were optimized by orthogonal experiments. The in vitro release characteristics of nanoparticles were studied by dynamic membrane dialysis. Results The prepared nanoparticles were relatively uniform spheroidal particles with an average particle size of about 124. 3 nm, a Zeta potential of - 20. 6 mV, and an average encapsulation efficiency of (44.72 ± 0.38%). In vitro drug release experiments showed that the particle burst release was less than 30% at 2 h, and the drug was slowly released within 48 h after burst release.

scholarly journals Refining the in vitro release test method for a dapivirine-releasing vaginal ring to match in vivo performance

2021 ◽  
Author(s):  
Diarmaid J. Murphy ◽  
Deanna Lim ◽  
Ryan Armstrong ◽  
Clare F. McCoy ◽  
Yahya H. Dallal Bashi ◽  
...  
Keyword(s):  
In Vitro Release ◽  
Water Soluble ◽  
Test Method ◽  
Vaginal Ring ◽  
Water Medium ◽  
In Vivo Release ◽  
Release Test ◽  
Vitro Release

AbstractPreviously reported in vitro release test methods for drug-releasing vaginal rings containing poorly water-soluble drugs have described use of water-alcohol systems or surfactant solutions in efforts to maintain sink conditions. Here, as part of efforts to more closely match in vitro and in vivo release for the 25 mg dapivirine matrix-type silicone elastomer vaginal ring for HIV prevention, we have investigated alternatives to the 1:1 v/v water/isopropanol medium described previously. Specifically, we evaluated dapivirine release from rings into (i) monophasic water/isopropanol mixtures of varying compositions and (ii) biphasic buffer/octanol systems using pH 4.2 and pH 7.0 buffers. The rate and mechanism of dapivirine release were dependent upon the isopropanol concentration in the release medium, in accordance with the observed trend in drug solubility. At 0 and 10% v/v isopropanol concentrations, dapivirine release followed a partition-controlled mechansim. For media containing ≥ 20% v/v isopropanol, in vitro release of dapivirine was significantly increased and obeyed permeation-controlled kinetics. Cumulative release of ~3.5 mg dapivirine over 28 days was obtained using a water isopropanol mixture containing 20% v/v isopropanol, similar to the ~4 mg dapivirine released in vivo. Dapivirine release into the biphasic buffer/octanol system (intended to mimic the fluid/tissue environment in vivo) was constrained by the limited solubility of dapivirine in the buffer component in which the ring resided, such that cumulative dapivirine release was consistently lower than that observed with the 20% v/v isopropanol in water medium. Release into the biphasic system was also pH dependent, in line with dapivirine’s pKa and with potential implications for in vivo release and absorption in women with elevated vaginal pH. Graphical abstract

scholarly journals Iron Complexation to Histone Deacetylase Inhibitors SAHA and LAQ824 in PEGylated Liposomes Can Considerably Improve Pharmacokinetics in Rats

2015 ◽  
Vol 17 (4) ◽  
pp. 583 ◽  
Author(s):  
Yan Wang ◽  
Sheng Tu ◽  
Dana Steffen ◽  
May Xiong
Keyword(s):  
Encapsulation Efficiency ◽  
Histone Deacetylase Inhibitors ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Pegylated Liposomes ◽  
Pharmacokinetic Properties ◽  
Fe Complexes ◽  
Vitro Release

PURPOSE. The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

1987 ◽  
Vol 57 (02) ◽  
pp. 201-204 ◽  
Author(s):  
P Y Scarabin ◽  
L Strain ◽  
C A Ludlam ◽  
J Jones ◽  
E M Kohner
Keyword(s):  
In Vitro Release ◽  
Mean Value ◽  
Reliable Estimate ◽  
Diabetic Patients ◽  
Single Measurement ◽  
Diabetic Population ◽  
The Difference ◽  
Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

Development, in vitro and in vivo Evaluations of Solid-Lipid Microparticles based on Solidified Micellar Carrier System for Oral Delivery of Cefepime

2017 ◽  
Vol 10 (1) ◽  
pp. 3582-3593
Author(s):  
Chukwuebuka Umeyor ◽  
Uchechukwu Nnadozie ◽  
Anthony Attama
Keyword(s):  
Oral Delivery ◽  
In Vitro Release ◽  
Carrier System ◽  
Solid Lipid ◽  
Solid Lipid Microparticles ◽  
Release Study ◽  
Lipid Microparticles ◽  
Vitro Release

This study seeks to formulate and evaluate a solid lipid nanoparticle-based, solidified micellar carrier system for oral delivery of cefepime. Cefepime has enjoyed a lot of therapeutic usage in the treatment of susceptible bacterial infections; however, its use is limited due to its administration as an injection only with poor patient compliance. Since oral drug administration encourage high patient compliance with resultant effect in improved therapy, cefepime was formulated as solid lipid microparticles for oral delivery using the concept of solidified micellar carrier system. The carrier system was evaluated based on particle yield, particle size and morphology, encapsulation efficiency (EE %), and thermal analysis using differential scanning calorimeter (DSC). Preliminary microbiological studies were done using gram positive and negative bacteria. In vitro release study was performed using biorelevant media, while in vivo release study was performed in white albino rats. The yield of solid lipid microparticles (SLM) ranged from 84.2 – 98.0 %. The SLM were spherical with size ranges of 3.8 ± 1.2 to 42.0 ± 1.4 µm. The EE % calculated ranged from 83.6 – 94.8 %. Thermal analysis showed that SLM was less crystalline with high potential for drug entrapment. Microbial studies showed that cefepime retained its broad spectrum anti-bacterial activity. In vitro release showed sustained release of cefepime from SLM, and in vivo release study showed high concentration of cefepime released in the plasma of study rats. The study showed that smart engineering of solidified micellar carrier system could be used to improve oral delivery of cefepime.

Formulation and Evaluation of Itopride Hydrochloride Floating Beads for Gastroretentive Delivery

2013 ◽  
Vol 6 (4) ◽  
pp. 2269-2280
Author(s):  
Nagratna Dhople ◽  
P N Dandag ◽  
A P Gadad ◽  
C K Pandey ◽  
Masthiholimath V S
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Sustained Release Formulation ◽  
Prokinetic Drug ◽  
Drug Entrapment Efficiency ◽  
Itopride Hydrochloride ◽  
Vitro Release

A gastroretentive sustained release system of itopride hydrochloride was formulated to increase the gastric residence time and modulate its release behavior. Itopride hydrochloride is a prokinetic drug used in the treatment of gastroeosophageal reflux disease, Non-ulcer dyspepsia and as an antiemetic. Hence, itopride hydrochloride beads were prepared by emulsion gelation method by employing low methoxy pectin and sodium alginate as sustained release polymers in three different ratios alone and in combination and sunflower oil was used to enable floating property to the beads. The effect of variation in polymer and their concentration was investigated. The beads were evaluated for production yield, particle size, swelling index, density measurement, buoyancy, drug content, drug entrapment efficiency, in vitro release characteristics and release kinetic study. Based on drug entrapment efficiency, buoyancy, swelling and in vitro release, F9 was selected as the optimized formulation. F9 was further subjected to surface morphology by SEM, in vitro release comparison with marketed formulation, in vivo floating study in rabbits and stability study for 90 days. In vitro release follows zero order and fitted in Korsmeyer peppas model (Non-Fickian release). Therefore, the rate of drug release is due to the combined effect of drug diffusion and polymer swelling. The in vivo X-ray studies revealed that the beads were floating in the rabbit stomach up to 10 hours. Thus, it was concluded that the sustained release formulation containing itopride hydrochloride was found to improve patient compliance, minimize the side effects and decrease the frequency of administration.

Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole

2020 ◽  
Vol 26 (14) ◽  
pp. 1543-1555 ◽  
Author(s):  
Meltem E. Durgun ◽  
Emine Kahraman ◽  
Sevgi Güngör ◽  
Yıldız Özsoy
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Size Distribution ◽  
Encapsulation Efficiency ◽  
Fungal Infections ◽  
In Vitro Release ◽  
Pluronic F127 ◽  
Glycol Succinate ◽  
Vitro Release

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.

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