Enhanced Pharmacokinetic Activity of Zotepine via Nanostructured Lipid Carrier System in Wistar Rats for Oral Application

2020 ◽  
Vol 8 (2) ◽  
pp. 148-160 ◽  
Author(s):  
Cernam Tirumalesh ◽  
Dinesh Suram ◽  
Narendar Dudhipala ◽  
Nagaraj Banala
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Wistar Rats ◽  
Water Solubility ◽  
In Vitro Release ◽  
Log P ◽  
Nanostructured Lipid Carrier ◽  
Vitro Release ◽  
Sem Studies

Background: Zotepine (ZT) is a substituted dibenzothiepine tricyclic molecule and second generation antipsychotic drug. It is available as the parenteral and oral solid dosage form, but, orally administered ZT has a poor oral bioavailability (10%) that might be due to either poor water solubility, high lipophilicity (Log P 4) and also first-pass hepatic metabolism. Objective: The oral bioavailability of ZT was improved by loading into a nanostructured lipid carriers (NLCs) system. Methods: Hot homogenization with probe sonication method was used for the preparation of ZT-NLCs formulations and characterized for an optimal system based on physicochemical characteristics and in vitro release. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized ZT-NLC formulation. The physical stability of the optimized ZT-NLC formulation was evaluated at the refrigerator and room temperature over two months. Furthermore, in vivo pharmacokinetic (PK) studies of optimized ZT-NLC and ZT coarse suspension (ZT-CS) as control formulation, were conducted in male Wistar rats. Results: The optimized formulation of ZT-NLC showed Z-avg, PDI, ZP of 145.8 ± 2.5 nm, 0.18 ± 0.05, -31.6 ± 1.8 mV, respectively. In vitro release studies indicated the sustained release of ZT. DSC and XRD studies revealed the conversion of ZT into an amorphous form. SEM studies showed the spherical shape of the ZT-NLC formulation. PK studies showed 1.8-folds improvement (p<0.05) in oral bioavailability when compared with ZTCS formulation. Conclusion: Overall, the results established that NLCs could be used as a new alternative delivery vehicle for the oral delivery of ZT.

scholarly journals Enhancement of Oral Bioavailability of Puerarin by Polybutylcyanoacrylate Nanoparticles

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Lixia Zhao ◽  
Anchang Liu ◽  
Min Sun ◽  
Jinsong Gu ◽  
Haigang Wang ◽  
...  
Keyword(s):  
Zeta Potential ◽  
Oral Bioavailability ◽  
Oral Delivery ◽  
Drug Carrier ◽  
In Vitro Release ◽  
Spherical Shape ◽  
Oral Drug ◽  
Burst Release ◽  
Vitro Release

The interest using novel drug delivery systems to improve oral bioavailability of drug with poor solubility is increasing. In this study, a new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of puerarin (PUE). PUE-loaded PBCN was successfully prepared by anionic polymerization method. Characterization of PUE-loaded PBCN was evaluated with morphology, size, zeta potential, and in vitro release study. The PBCN loading PUE exhibited a spherical shape under transmission electron microscopy with an average size of 159.4 nm, and the zeta potential was −15.0 mV. The in vitro release of PUE-loaded PBCN showed an initial burst release followed by a sustained release. Physicochemical state of PUE in PBCN was investigated by differential scanning colorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. The results indicated that PUE in PBCN was in a noncrystalline state. The oral pharmacokinetic study in rats showed that the relative bioavailability of PUE-encapsulated PBCN to the crude PUE was more than 550%. It can be concluded that PBCN as an oral drug carrier can significantly improve the oral bioavailability of PUE.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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.

scholarly journals Self microemulsifying powder using Aerosil as a carrier

2021 ◽  
Vol 56 (2) ◽  
pp. 141-146
Author(s):  
N Arju ◽  
PK Bara ◽  
MT Amin ◽  
DR Bhowmik ◽  
MS Hossain
Keyword(s):  
Oral Delivery ◽  
Evaluation Studies ◽  
In Vitro Release ◽  
Study Drug ◽  
Evaluation Study ◽  
Flowing Powder ◽  
Uv Visible ◽  
Short Time ◽  
Vitro Release

This investigation highlighted the development of a solid self micro emulsifying drug delivery system (solid SMEDDS) for improved oral delivery of Valsartan. Liquid SMEDDS were formulated and then the liquid formulation was transformed into free-flowing powder by adsorption on a solid carrier. Here the formulations were prepared in various ratios of the drug to the excipients. Various evaluation studies were performed. In-vitro release profiles of all formulations were evaluated. The concentration of the diffused drug was measured using a UV-visible spectrophotometer at λmax= 250 nm. The faster dissolution was exhibited by the formulations containing Avicel. The experimental results for prepared solid-SMEDDS showed the improved dissolution of the study drug in a short time. F-3 (Assay:77%; Dissolution: 51.7% after 45 min, 63% after 60 min) and F-4 (Assay:63%; Dissolution: 49.1% after 45 min, 67% after 60 min) showed better evaluation study and this two might be formulated in future. Thus, this study revealed the formulation solid-SMEDDS using Aerosil 200 as an adsorbent with the potential of enhancing the solubility, and dissolution rate of the drug. Bangladesh J. Sci. Ind. Res.56(2), 141-146, 2021

Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles

2015 ◽  
Vol 8 (1) ◽  
pp. 2779-2785
Author(s):  
Kishan V ◽  
Suvarna G ◽  
Narender D
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Bioavailability ◽  
Phosphate Buffer ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Release Studies ◽  
First Pass ◽  
Vitro Release ◽  
Rosuvastatin Calcium

Rosuvastatin calcium (RC), is a hypolipidemic drug, and has poor oral bioavailability of about 20% due to first-pass effect. For improving the oral bioavailability of RC, solid lipid nanoparticles (SLNs) were developed using triglycerides (tristearin, tripalmitin, and trimyristin). Hot homogenization followed by ultrasonication method was used to prepare RC-SLNs. The prepared SLNs were characterized for particle size, PDI, zeta potential (ZP), entrapment efficiency (EE) and drug content. In vitro release studies were performed in 0.1N HCl and pH 6.8 phosphate buffer of by open tube method. Physical stability the SLNs was observed at refrigerated temperature and room temperature for 60 days. Pharmacokinetics of RC- SLNs after oral administration, in male Wistar rats was studied. SLNs prepared with tristearin (Dyanasan-118) having size of 207.3 ± 8.52 nm, PDI of 0.344 ± 0.084, ZP of – 20.9 ± 4.88 mV with 97.06 ± 0.210 % EE were optimized. Differential scanning calorimetric (DSC) study revealed that no interaction between drug and lipid. In vitro release studies showed that more cumulative release of RC in     pH 6.8 phosphate buffer than in 0.1NHCl during 24 hours. The lyophilized SLN formulation was used in knowing morphology of SLNs and was found to have spherical shape with increased polydispersity by Scanning electron microscopy. Pharmacokinetic studies showed the relative oral bioavailability of SLNs was 2.2 fold when compared to that of a suspension (p<0.001). Taken together, the results are indicative of SLNs as lipid based carriers for improving the oral bioavailability of this drug by minimizing first pass metabolism.

scholarly journals OPTIMIZATION AND CHARACTERIZATION OF ION ACTIVATED OCULAR IN-SITU GEL FORMULATION FOR BACTERIAL CONJUNCTIVITIS

2020 ◽  
pp. 182-191
Author(s):  
ANKITA KAPOOR ◽  
G. D. GUPTA
Keyword(s):  
Research Work ◽  
In Vitro Release ◽  
Gellan Gum ◽  
Log P ◽  
Eye Drops ◽  
Bacterial Conjunctivitis ◽  
In Situ Gel ◽  
Vitro Release

Objective: The present research work aims at describing the formulation, optimization and evaluation of ion activated ocular in-situ gel of gatifloxacin for treatment of bacterial conjunctivitis so as to overcome patient inconvenience, precorneal drug elimination, variation in efficacy, vision blurring and frequent instillation associated with conventional eye drops and ointments. Methods: In-situ gel was prepared using gellan gum as an ion activated phase transition polymer and HPMC K100M as release retardant. Gatifloxacin was characterized by spectrophotometry. Crystalline state of the drug was determined using X Ray Diffraction study. The developed formulation exhibited instantaneous gel formation in simulated lacrimal fluid (pH 7.4), which was further evaluated for its rheology, irritancy parameters, in vitro release, trans-corneal permeation and antimicrobial activity. Results: Gatifloxacin exhibited λmax 286 nm obeying Beer Lambert’s law and pH-dependent solubility at a pH range of 2 to 4. 0.6% gellan gum and 0.4% HPMC K100M were optimized in the formulation which exhibited a viscosity of 55 cps in sol form and 325 cps in gel form with pseudoplastic behavior and prolonged in vitro release. Permeation of formulation was 75.8% in 7 h with log P of drug 0.59. Developed isotonic and non-irritant formulation had a lower apparent permeability coefficient of 8.15 x 10-5 cm/sec as compared to marketed formulation. Conclusion: A Formulation can be viewed as an efficacious medicine by virtue of its higher zone of inhibition, ability to enhance precorneal residence time and consequently ocular bioavailability with lesser frequency of administration attributed to slow and prolonged diffusion of the drug from the polymeric solutions.

scholarly journals Nanoemulsion for Solubilization, Stabilization, and In Vitro Release of Pterostilbene for Oral Delivery

2014 ◽  
Vol 15 (4) ◽  
pp. 1000-1008 ◽  
Author(s):  
Yue Zhang ◽  
Zhenhua Shang ◽  
Chunhui Gao ◽  
Man Du ◽  
Shixia Xu ◽  
...  
Keyword(s):  
Oral Delivery ◽  
In Vitro Release ◽  
Vitro Release

scholarly journals Optimizing Prednisolone Loading into Distiller’s Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery

Pharmaceutics ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 17 ◽  
Author(s):  
Esther T. L. Lau ◽  
Stuart K. Johnson ◽  
Barbara A. Williams ◽  
Deirdre Mikkelsen ◽  
Elizabeth McCourt ◽  
...  
Keyword(s):  
Oral Delivery ◽  
In Vitro Release ◽  
Vitro Release

scholarly journals Fucoxanthin@Polyvinylpyrrolidone Nanoparticles Promoted Oxidative Stress-Induced Cell Death in Caco-2 Human Colon Cancer Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 92
Author(s):  
Yue Sui ◽  
Yue Gu ◽  
Yujing Lu ◽  
Chenxu Yu ◽  
Jie Zheng ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Water Solubility ◽  
In Vitro Release ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Functional Activities ◽  
Human Colon Cancer Cells ◽  
Vitro Release

Fucoxanthin (FX), a natural carotenoid found in seaweed with multiple functional activities, is unstable with a poor water solubility that limits its utilization. This study aimed to improve FX’s stability and bioavailability via the nano-encapsulation of FX in polyvinylpyrrolidone (PVP)-coated FX@PVP nanoparticles (NPs). The FX@PVP NPs were evaluated in terms of their morphology, stability, encapsulation efficiency (EE), loading capacity (LC), and in vitro release to optimize the encapsulation parameters, and a 1:8 FX:PVP ratio was found to perform the best with the highest EE (85.50 ± 0.19%) and LC (10.68 ± 0.15%) and improved FX stability. In addition, the FX@PVP NPs were shown to effectively deliver FX into Caco-2 cancer cells, and the accumulation of FX in these cancer cells showed pro-oxidative activities to ameliorate H2O2-induced damage and cell death. The FX@PVP NPs could potentially become a new therapeutical approach for targeted cancer treatment.

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