scholarly journals IVIVC from Long Acting Olanzapine Microspheres

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Susan D'Souza ◽  
Jabar A. Faraj ◽  
Stefano Giovagnoli ◽  
Patrick P. DeLuca
Keyword(s):  
Drug Release ◽  
Rank Order ◽  
Plga Microsphere ◽  
Release Rates ◽  
Proper Selection ◽  
Long Acting ◽  
Selection Of ◽  
Release Profiles

In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of theirin vitrobehavior at 37°C, using a dialysis based method, with the goal of obtaining an IVIVC.In vivoprofiles were determined by deconvolution (Nelson-Wagner method) and using fractional AUC. Thein vitroandin vivorelease profiles exhibited the same rank order of drug release. Further,in vivoprofiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that thein vitroprofile lagged slightly behindin vivorelease, but the results were not statistically significant (P<0.0001). Using the four formulations that exhibited different release rates, a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1 : 1 correlation (R2>0.96) betweenin vitrorelease andin vivomeasurements confirmed the excellent relationship betweenin vitrodrug release and the amount of drug absorbedin vivo. The results of this study suggest that proper selection of anin vitromethod will greatly aid in establishing a Level A IVIVC for long acting injectables.

scholarly journals Determining drug release rates of hydrophobic compounds from nanocarriers

2016 ◽  
Vol 374 (2072) ◽  
pp. 20150128 ◽  
Author(s):  
Suzanne M. D’Addio ◽  
Abdallah A. Bukari ◽  
Mohammed Dawoud ◽  
Heike Bunjes ◽  
Carlos Rinaldi ◽  
...  
Keyword(s):  
Drug Release ◽  
Magnetic Separation ◽  
Lipid Membranes ◽  
Separation Efficiency ◽  
Release Kinetics ◽  
Release Rates ◽  
Assay Protocol ◽  
Release Profiles

Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitro assay protocol based on ‘lipid sinks’ and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo , facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating. This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.

scholarly journals Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 736
Author(s):  
Sharif Md Abuzar ◽  
Eun Jung Park ◽  
Yeji Seo ◽  
Juseung Lee ◽  
Seung Hyuk Baik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Release ◽  
Entrapment Efficiency ◽  
Lag Phase ◽  
Burst Release ◽  
Sustained Drug Release ◽  
Long Acting ◽  
High Entrapment Efficiency

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.

scholarly journals Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-27 ◽  
Author(s):  
Silvia Baiguera ◽  
Luca Urbani ◽  
Costantino Del Gaudio
Keyword(s):  
Tissue Engineering ◽  
Positive Outcome ◽  
Great Effort ◽  
Huge Number ◽  
Proper Selection ◽  
Specific Strategy ◽  
Selection Of

It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging fromin vitrotoin vivostudies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring toin vivoinvestigations. In this regard, the present paper aims to review the results ofin vivotissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome.

scholarly journals In Vitro–In Vivo Correlation (IVIVC) Population Modeling for the In Silico Bioequivalence of a Long-Acting Release Formulation of Progesterone

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 255
Author(s):  
Elena M. Tosca ◽  
Maurizio Rocchetti ◽  
Elena Pérez ◽  
Conchi Nieto ◽  
Paolo Bettica ◽  
...  
Keyword(s):  
Clinical Studies ◽  
In Vitro Release ◽  
Release Formulation ◽  
Mixed Effect ◽  
Ring Model ◽  
Long Acting ◽  
Vitro Release ◽  
Release Profiles

Health authorities carefully evaluate any change in the batch manufacturing process of a drug before and after regulatory approval. In the absence of an adequate in vitro–in vivo correlation (Level A IVIVC), an in vivo bioequivalence (BE) study is frequently required, increasing the cost and time of drug development. This study focused on developing a Level A IVIVC for progesterone vaginal rings (PVRs), a dosage form designed for the continuous delivery in vivo. The pharmacokinetics (PK) of four batches of rings charged with 125, 375, 750 and 1500 mg of progesterone and characterized by different in vitro release rates were evaluated in two clinical studies. In vivo serum concentrations and in vitro release profiles were used to develop a population IVIVC progesterone ring (P-ring) model through a direct differential-equation-based method and a nonlinear-mixed-effect approach. The in vivo release, Rvivo(t), was predicted from the in vitro profile through a nonlinear relationship. Rvivo(t) was used as the input of a compartmental PK model describing the in vivo serum concentration dynamics of progesterone. The proposed IVIVC P-ring model was able to correctly predict the in vivo concentration–time profiles of progesterone starting from the in vitro PVR release profiles. Its internal and external predictability was carefully evaluated considering the FDA acceptance criteria for IVIVC assessment of extended-release oral drugs. Obtained results justified the use of the in vitro release testing in lieu of clinical studies for the BE assessment of any new PVRs batches. Finally, the possible use of the developed population IVIVC model as a simulator of virtual BE trials was explored through a case study.

scholarly journals Factors Contributing to Drug Release From Enteric-Coated Omeprazole Capsules: An In Vitro and In Vivo Pharmacokinetic Study and IVIVC Evaluation in Beagle Dogs

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090898
Author(s):  
Cheng Cui ◽  
Jiabei Sun ◽  
Xueqing Wang ◽  
Zhenxi Yu ◽  
Yaqin Shi
Keyword(s):  
Drug Release ◽  
Critical Factor ◽  
Pharmacokinetic Studies ◽  
Beagle Dogs ◽  
Enteric Coating ◽  
Coating Materials ◽  
Enteric Coated ◽  
Release Profiles

This study was performed to explore factors influencing the release of the proton pump inhibitor omeprazole from enteric-coated capsules in vitro and absorption in vivo in beagle dogs. Enteric-coated pellets with different enteric coating materials and coating levels were designed and prepared. All self-prepared formulations were characterized in vitro as well as in vivo and compared to the brand and generic commercial products. Evaluation of the corresponding release profiles suggested that coating material was the most critical factor. Enteric coating level determined the lag time before initiation of drug release, and subcoating level affected the drug release rate. Pharmacokinetic studies were performed in beagle dogs to further confirm the influence of formulation factors on drug absorption. Medium at pH 6.8 was a more biorelevant condition for in vitro drug release tests, although medium at pH 6.0 was better for discriminating release profiles of different formulations. A multiple level C in vitro/in vivo correlation was preliminarily established by which Tmax and Cmax of omeprazole formulations could be predicted with release parameters such as Tlag and T25. These results may facilitate quality evaluation and potentially improve the clinical efficacy of generic omeprazole products.

scholarly journals Effect of Different Carriers on In vitro and In vivo Drug Release Behavior of Aceclofenac Proniosomes

2021 ◽  
Vol 18 ◽  
Author(s):  
Rana M.F. Sammour ◽  
Bappaditya Chatterjee ◽  
Muhammad Taher ◽  
Mohammed S.M. Saleh ◽  
Aliasgar Shahiwala
Keyword(s):  
Drug Release ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Albino Rats ◽  
In Vitro Drug Release ◽  
Release Studies ◽  
Pure Drug ◽  
Selection Of

Background: Improved bioavailability of Aceclofenac (ACE) may be achieved through proniosomes, which is considered as one of the most effective drug delivery systems and is expected to represent a valuable approach for the development of a better oral dosage form as compared to the existing product. However, the carrier in this system plays a vital role to control the drug release and modulate drug dissolution. Accordingly, a comparative study between different carriers can give clear ideas on the selection of carriers to prepare ACE proniosomes. Objective: This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers on in vitro and in vivo performance of Aceclofenac (ACE) proniosomes. Methods: Three formulations of proniosomes were prepared by the slurry method using the 100 mg ACE, 500 mg Span 60, 250 mg Cholesterol with 1300mg of different carriers, i.e., Glucose (FN1), Maltodextrin (FN2), and Mannitol (FN3). In vitro, drug release studies were conducted by the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography (HPLC) method, and data were evaluated using further kinetic and statistical tools. Results: No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were used as such for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved drug was found to be 42% for the pure drug, while 70%, 17% 30% for FN1, FN2, and FN3 respectively at 15 min. After 24 hrs, the pure drug showed a maximum of 50 % release while 94%, 80%, 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in vivo study conducted using albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin and glucose as carriers compared to the pure drug was 183% and 112% respectively. Mannitol based formulation exhibited low bioavailability (53.7%) may be attributed to its osmotic behavior. Conclusion: These findings confirm that a carrier plays a significant role in determining in vitro and in vivo performance of proniosomes and careful selection of carrier is an important aspect of proniosomes optimization.

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