Probucol Self-Emulsified Drug Delivery System: Stability Testing and Bioavailability Assessment in Human Volunteers

2019 ◽  
Vol 16 (4) ◽  
pp. 325-330
Author(s):  
Abdelazim Zaghloul ◽  
Ahmed Lila ◽  
Fathy Abd-Allah ◽  
Aly Nada
Keyword(s):  
Drug Delivery ◽  
Soybean Oil ◽  
Drug Delivery System ◽  
Delivery System ◽  
Relative Bioavailability ◽  
System Stability ◽  
Pharmacokinetic Parameters ◽  
Human Volunteers ◽  
The Stability

Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability. Objective: The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers. Methods: The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference). Results: The results showed that formulations (F1-F4) were stable if stored at 20 °C. The mean (n=3) pharmacokinetic parameters for stable formulations were: The Cmax, 1070.76, 883.16, 2876.43, 3513.46 and 1047.37 ng/ml; the Tmax, 7.93, 7.33, 3.96, 3.67 and 4.67 hr.; the AUC (0-t), 41043.41, 37763.23, 75006.26, 46731.36 and 26966.43 ng.hr/ml for F1, F2, F3, F4 and reference, respectively. The percentage relative bioavailability was in this order: F3> F4> F1> F2>. Conclusion: In conclusion, the PBSEDDS formulations were stable at room temperature. F4 showed the highest Cmax and the shortest Tmax. All the formulations showed significant enhancement of bioavailability compared with the reference. The results illustrated the potential use of SEDDS for the delivery of probucol hydrophobic compound.

scholarly journals Enhanced Dissolution and Oral Bioavailability of Cyclosporine A: Microspheres Based on αβ-Cyclodextrins Polymers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 285 ◽  
Author(s):  
Malika Lahiani-Skiba ◽  
Francois Hallouard ◽  
Frederic Bounoure ◽  
Nicolas Milon ◽  
Youness Karrout ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Secondary Structure ◽  
Oral Administration ◽  
Drug Delivery System ◽  
Delivery System ◽  
Cyclosporine A ◽  
Polymer Mixture ◽  
Pharmacokinetic Parameters

Cyclosporine (CsA) has a selective property of suppressing various T-lymphocyte functions. This is of utmost importance in preventing allograft rejection by several organ transplantations, as well as in the treatment of systemic and local autoimmune disorders. However, the poor water solubility of CsA can be a major hurdle for its absorption into the blood stream, which leads to low bioavailability and thus less efficacy. The aim of this study was to prepare, characterize, and evaluate in vitro as well as in vivo, the potential of the innovative CsA drug delivery system. The latter contains CsA in spherical amorphous solid dispersion (SASD) which is embedded in an original α-cyclodextrin and β-cyclodextrin polymer mixture (Poly-αβ-CD) as a multifunctional amorphous carrier. The new developed SASD formulation showed that CsA was molecularly dispersed in αβ-cyclodextrins in an amorphous form, as was confirmed by physicochemical characterization studies. Interestingly, the peptide secondary structure, and thus, the drug activity was not impacted by the preparation of SASD as was shown by circular dichroism. Furthermore, the in vitro CsA release profile kinetics was almost identical to the commercially available product Neoral®. This study presents the first in vivo proof-of-concept for a novel drug delivery system based on Poly-αβ-CD containing CsA, with SASD allowing for increased bioavailibility. The pharmacokinetic parameters of cyclosporine A from the spherical spray-dried dispersion formulation was demonstrated in a “rat” animal model. For comparison, the commercially available Neoral® was studied. Importantly, the pharmacokinetic parameters were improved by extending Tmax from 2 to 3 h after the oral administration in rats, and eventually preventing the enterohepatic circulation. All these results clearly demonstrate the improved pharmacokinetic parameters and enhanced bioavailability of CsA in the new developed drug delivery system. These data demonstrated the superiority of the newly developed Poly-αβ-CD formulation for oral administration of the poorly soluble CsA in vivo without altering its secondary structure. Poly-αβ-CD can be a very useful tool for the oral administration of poorly water-soluble drugs.

Enhancement of Nimodipine Solubility by Self-Nano-emulsifying Drug Delivery System

2019 ◽  
Vol 12 (5) ◽  
pp. 4648-4656
Author(s):  
Suresh Gande ◽  
S. Srikanth Reddy ◽  
Bhikshapathi D. V. R. N.
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Drug Delivery System ◽  
Delivery System ◽  
Spherical Shape ◽  
Drug Dissolution ◽  
The Stability

Self-nanoemulsifying drug delivery system (SNEDDS) of Nimodipine was developed with the purpose of improving the bioavailability of the drug. Based on the results of Nimodipine solubility studies Peceol, Transcutol P and PEG 400 were optimized as oil, surfactant and co-surfactant for the formulation and Pseudo ternary plots was constructed by Chemix software. Fifteen formulations of Nimodipine SNEDDS prepared and analyzed for particle size, emulsification time, percentage drug release, percentage transmittance, in vitro drug dissolution studies and thermodynamic stability. The optimized Nimodipine SNEDDS formulation (F13) subjected to drug-excipient compatibility studies by FTIR. They are analyzed for zeta potential, SEM and stability. The particle size of optimized Nimodipine SNEDDS formulation was 25.9 nm, PDI is 0.382 and zeta potential -12.7 mV that are optimal for the stability of emulsion. SEM studies of Nimodipine SNEDDS indicated spherical shape and uniform particle distribution. The drug release of formulation F13 (98.25±4.77%) was higher than pure drug (38.49±3.88%). The stability studies indicated no change in drug content, drug release, emulsifying properties and appearance. Hence a potential SNEDDS formulation of Nimodipine developed with increased dissolution rate, bioavailability and solubility.

scholarly journals The Evaluation of Proanthocyanidins/Chitosan/Lecithin Microspheres as Sustained Drug Delivery System

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hong-Li Yu ◽  
Zhan-Qin Feng ◽  
Jing-Jing Zhang ◽  
Yong-Hong Wang ◽  
De-Jun Ding ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
In Vitro Release ◽  
Sustained Drug Delivery ◽  
Swelling Rate ◽  
Drying Technology ◽  
The Stability

Proanthocyanidin (PC) has attracted wide attention on cosmetics and pharmaceutical due to its antioxidant, anticancer, antimicrobial, antiangiogenic, and anti-inflammatory activities. However, PC applications are limited because of its sensitivity to thermal treatment, light, and oxidation and the poor absorption in the gastrointestinal tract. Thus, a novel dosage form of PC needs to be designed to improve its stability and bioavailability for drug delivery. The objective of this study is to fabricate proanthocyanidins/chitosan/lecithin (PC/CTS/LEC) microspheres and investigate various characteristics. In the current study, PC/CTS/LEC microspheres were prepared by spray-drying technology. The yield (61.68%), encapsulation efficiency (68.19%), and drug loading capacity (17.05%) were found in the results. The scanning electron microscope demonstrated that the microspheres were spherical in shape with wrinkled surfaces. DSC study displayed that the microspheres stability was greatly improved when comparing with bare PC. The in vitro release study showed that the 76.92% of PC was released from microspheres within 48 h. The moisture contents of microspheres ranged from 8% to 13%. The swelling rate and tapped density of microspheres were elevated with increasing the concentration of chitosan in the formulations. The moisture uptake of microspheres was saturated at 40°C/RH75% within 12 h. Our results indicated that the stability of PC/CTS/LEC microspheres was enhanced, and it is a promising carrier for sustained drug delivery system.

scholarly journals Applicability of Gum Karaya in the Preparation and in Vitro Evaluation of Losartan Potassium as Chronotherapeutic Drug Delivery System

2015 ◽  
Vol 7 (1-2) ◽  
pp. 65-74
Author(s):  
K. Latha ◽  
V. V. Srikanth ◽  
S. A. Sunil ◽  
N. R. Srinivasa ◽  
M. U. Uhumwangho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tensile Strength ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lag Time ◽  
Losartan Potassium ◽  
In Vitro Dissolution ◽  
Burst Release ◽  
Gum Karaya

The objective of this investigation is to study the applicability of gum karaya, the natural gum for the preparation and in vitro evaluation of losartan potassium, as Chronotherapeutic Drug Delivery System (ChDDS). The compression-coated timed-release tablets (CCT) containing losartan potassium in the core tablet were prepared by dry coating technique with different ratios of gum karaya as the outer coat. The parameters investigated were tensile strength, friability, in vitro dissolution studies and drug concentration. The optimized formulation was further characterized by powder XRD and FTIR to investigate interactions and no interactions observed. The tensile strength and friability of all the CCT were between 1.06-1.23 MN/m2 and < 0.3% respectively.  All the CCT showed a clear lag time before a burst release of drug. However, the lag time of drug release increased as the amount of gum karaya in the outer layer increased. For instance, the lag time of LGK1, LGK2, LGK3, LGK4, LGK5, LGK6 and LGK7 were 16, 10.5, 5.5, 3, 2, 1.5 and 0.5 hrs respectively.  The drug content of all the CCT was >98%. Formulation LGK3 was taken as an optimized formulation which can be exploited to achieve ChDDS of losartan potassium for the treatment of hypertension. 

Excipient effects on in vitro cytotoxicity of a novel paclitaxel self‐emulsifying drug delivery system

2003 ◽  
Vol 92 (12) ◽  
pp. 2411-2418 ◽  
Author(s):  
Neslihan Gursoy ◽  
Jean‐Sebastien Garrigue ◽  
Alain Razafindratsita ◽  
Gregory Lambert ◽  
Simon Benita ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Vitro Cytotoxicity
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