scholarly journals Synthesis of Tilmicosin Nanostructured Lipid Carriers for Improved Oral Delivery in Broilers: Physiochemical Characterization and Cellular Permeation

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 315 ◽  
Author(s):  
Benazir Sahito ◽  
Qian Zhang ◽  
Haifeng Yang ◽  
Lin Peng ◽  
Xiuge Gao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Bioavailability ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Amorphous Structure ◽  
Nanostructured Lipid Carriers ◽  
Phosphate Solution ◽  
Lipid Matrix ◽  
Glycoprotein P ◽  
P Glycoprotein

This study aimed to develop nanostructured lipid carriers (NLCs) for improved oral absorption of tilmicosin (TMS) in broilers. Thus, palmitic acid, lauric acid, and stearic acid were selected as solid lipids to formulate TMS-pNLCs, TMS-lNLCs, and TMS-sNLCs, respectively. They showed similar physicochemical properties and meanwhile possessed excellent storage and gastrointestinal stability. The TMS interacted with the lipid matrix and was encapsulated efficiently in NLCs in an amorphous structure. NLCs could enhance oral absorption of TMS compared to 10% tilmicosin phosphate solution in broilers, among which the TMS-sNLCs were the most efficient drug delivery carriers, with a relative oral bioavailability of 203.55%. NLCs could inhibit the efflux of P-glycoprotein (P-pg) toward TMS, which may be involved with improved oral absorption. Taken together, these types of solid lipids influenced the enhanced level of NLCs toward oral bioavailability of TMS, and the sNLCs proved to be the most promising oral delivery carriers of TMS.

scholarly journals Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 68 ◽  
Author(s):  
Ching-Yun Hsu ◽  
Pei-Wen Wang ◽  
Ahmed Alalaiwe ◽  
Zih-Chan Lin ◽  
Jia-You Fang
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
Lymphatic Transport ◽  
Glycol Succinate ◽  
Gi Tract ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Antioxidant Agents ◽  
Lipid Nanocarriers ◽  
Delivery Efficiency

The chemical environment and enzymes in the gastrointestinal (GI) membrane limit the oral absorption of some vitamins. The GI epithelium also contributes to the poor permeability of numerous antioxidant agents. Thus, lipophilic vitamins do not readily dissolve in the GI tract, and therefore they have low bioavailability. Nanomedicine has the potential to improve the delivery efficiency of oral vitamins. In particular, the use of lipid nanocarriers for certain vitamins that are administered orally can provide improved solubility, chemical stability, epithelium permeability and bioavailability, half-life, nidus targeting, and fewer adverse effects. These lipid nanocarriers include self-emulsifying drug delivery systems (SEDDSs), nanoemulsions, microemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). The use of nontoxic excipients and sophisticated material engineering of lipid nanosystems allows for control of the physicochemical properties of the nanoparticles and improved GI permeation via mucosal or lymphatic transport. In this review, we highlight recent progress in the development of lipid nanocarriers for vitamin delivery. In addition, the same lipid nanocarriers used for vitamins may also be effective as carriers of vitamin derivatives, and therefore enhance their oral bioavailability. One example is the incorporation of d-α-tocopheryl polyethylene glycol succinate (TPGS) as the emulsifier in lipid nanocarriers to increase the solubility and inhibit P-glycoprotein (P-gp) efflux. We also survey the concepts and discuss the mechanisms of nanomedical techniques that are used to develop vitamin-loaded nanocarriers.

Development and Oral Bioavailability of Self-Emulsifying Formulation of Ketoconazole

2013 ◽  
Vol 5 (4) ◽  
pp. 1858-1865
Author(s):  
Arundhati Bhattacharyya ◽  
M Bajpai
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Aqueous Suspension ◽  
Droplet Diameter ◽  
Tween 80 ◽  
Concurrent Administration ◽  
System Maintenance ◽  
Pure Drug ◽  
Ph Dependent

Ketoconazole is an imidazole antifungal drug belonging to the class II of Biopharmaceutic Classification System. Maintenance of gastric acidity is essential for adequate dissolution and absorption of ketoconazole. Concurrent administration of antacid and antiulcer preparations decreases the oral absorption of ketoconazole often causing therapeutic failure.  The aim of this study was to evaluate whether a self-emulsifying formulation of ketoconazole would be able to overcome the pH dependent dissolution and oral bioavailability. Self-emulsifying drug delivery system (SEDDS) was prepared after selecting the oil, surfactant and co-surfactant by solubility analysis. Optimum ratio of the components was finalized on the basis of drug content, self-emulsification and mean droplet diameter. The effect of pH on dissolution was studied in comparison to the pure drug. Oral bioavailability was determined in comparison to aqueous suspension in rats and the effect of co-administration of ranitidine hydrochloride solution and a commercially available liquid antacid preparation was studied. The optimized formulation containing 20% Capryol 90 and 40% each of Carbitol and Tween 80, exhibited 100% drug release regardless of the pH whereas the pure drug exhibited a highly pH dependent dissolution. The AUC0-24 resulted with oral administration of the SEDDS formulation was about 34%, 43% and 60% higher compared to the aqueous suspension when administered alone, administered with ranitidine and administered with antacid respectively. The results of the present study demonstrate that self-emulsifying formulations can be utilized for oral delivery of weakly basic drugs like ketoconazole which exhibit pH dependent dissolution.

New and novel approaches for enhancing the oral absorption and bioavailability of protein and peptides therapeutics

2020 ◽  
Vol 11 (11) ◽  
pp. 713-732
Author(s):  
Abhishek Kanugo ◽  
Ambikanandan Misra
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Enzyme Inhibitors ◽  
Oral Route ◽  
Limited Success ◽  
Physical Chemical ◽  
Novel Approaches ◽  
Active Research

The advancement of the oral route for macromolecules has gained a lot of attention due to its noninvasive nature, safe and challenging in active research but with limited success. Oral administration poses challenges due to poor solubility, short half-life, quick elimination and the physical, chemical and biological barriers of the gastrointestinal tract. Approaches of past for improving oral absorption, such as enhancers, mucoadhesive delivery and enzyme inhibitors have been taken over by novel approaches like advanced liposomes, self-nanoemulsifying drug delivery system, nanoparticles and targeted delivery. Eudratech™ Pep, Peptelligence, Rani Pill and Pharm Film are the emerging technologies for delivering oral proteins and peptide. Calcitonin, semaglutide and octreotide are the peptides available in the market for oral delivery as outcomes of these technologies.

scholarly journals LC478, a Novel Di-Substituted Adamantyl Derivative, Enhances the Oral Bioavailability of Docetaxel in Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 135 ◽  
Author(s):  
Seung Han ◽  
Qili Lu ◽  
Kyeong Lee ◽  
Young Choi
Keyword(s):  
Oral Bioavailability ◽  
Oral Absorption ◽  
Ussing Chamber ◽  
Absolute Bioavailability ◽  
Time Curve ◽  
Glycoprotein P ◽  
Dose Concentration ◽  
Chamber Studies

P-glycoprotein (P-gp)-mediated efflux of docetaxel in the gastrointestinal tract mainly impedes its oral chemotherapy. Recently, LC478, a novel di-substituted adamantyl derivative, was identified as a non-cytotoxic P-gp inhibitor in vitro. Here, we assessed whether LC478 enhances the oral bioavailability of docetaxel in vitro and in vivo. LC478 inhibited P-gp mediated efflux of docetaxel in Caco-2 cells. In addition, 100 mg/kg of LC478 increased intestinal absorption of docetaxel, which led to an increase in area under plasma concentration-time curve (AUC) and absolute bioavailability of docetaxel in rats. According to U.S. FDA criteria (I, an inhibitor concentration in vivo tissue)/(IC50, inhibitory constant in vitro) >10 determines P-gp inhibition between in vitro and in vivo. The values 15.6–20.5, from (LC478 concentration in intestine, 9.37–12.3 μM)/(IC50 of LC478 on P-gp inhibition in Caco-2 cell, 0.601 μM) suggested that 100 mg/kg of LC478 sufficiently inhibited P-gp to enhance oral absorption of docetaxel. Moreover, LC478 inhibited P-gp mediated efflux of docetaxel in the ussing chamber studies using rat small intestines. Our study demonstrated that the feasibility of LC478 as an ideal enhancer of docetaxel bioavailability by P-gp inhibition in dose (concentration)-dependent manners.

P-Glycoprotein-Mediated Efflux Using a Rapidly Maturing Caco2 Clone (CLEFF4) in Only 5 Days without Requiring Modified Growth Medium

2020 ◽  
Vol 26 (1) ◽  
pp. 151-160
Author(s):  
Andrew Crowe
Keyword(s):  
Oral Absorption ◽  
Mdck Cells ◽  
Target Cells ◽  
Glycoprotein P ◽  
Caco2 Cells ◽  
P Glycoprotein ◽  
New Chemical Entities ◽  
Bidirectional Transport ◽  
Gp Model

In drug discovery it is essential that one of the parameters tested for any new chemical entity is its affinity for human efflux systems, most notably P-glycoprotein (P-gp). These efflux systems affect not only rates of oral absorption but also rates of excretion through the liver, blood–brain barrier, and accumulation in potential target cells that upregulate efflux systems. Current methods to determine drugs’ P-gp transport potential include in vitro bidirectional transport studies, and the two most common cell lines used are Caco2 and MDR1-transfected MDCK models. Caco2 cells are human but slow growing and require more than 3 weeks to mature, while MDCK cells are canine, but when transfected with human P-gp become a rapid model of P-gp affinity. Our laboratory has generated a Caco2 subclone called CLEFF4 that is fully human, yet now approaches the rapid nature of the MDCK model. No special medium is required. We have shown, in as little as 5 days postseeding, high transepithelial electrical resistance values of more than 1000 Ω·cm2 plus P-gp expression more than threefold higher than that of 21-day-old cells. Currently tested drugs included rhodamine 123 (Rh123), vinblastine, and doxorubicin, and all drugs exhibited P-gp-mediated efflux that was inhibited by PSC833. By day 6, bidirectional transport of Rh123 was as potent as that of mature Caco2 cells, for use in comparative P-gp affinity studies. We now have a human P-gp model that is rapid and works without any need for special accelerating medium. We believe this could be a welcome addition to the testing regime of new chemical entities.

scholarly journals Microsponges for controlled release and enhanced oral bioavailability of carbamazepine

2021 ◽  
Author(s):  
Karam F. Abdalla ◽  
Mohamed A. Osman ◽  
Ahmed T. Nouh ◽  
Gamal M. El Maghraby
Keyword(s):  
Sustained Release ◽  
Oral Bioavailability ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Scanning Calorimetry ◽  
Time Curve ◽  
Diffusion Technique ◽  
Optimum Formulation

Abstract The oral absorption and hence the oral bioavailability of carbamazepine (CBZ) is variable even after administration of rapidly dissolving formulation. This problem was attributed to supersaturation of CBZ and transformation to the less soluble carbamazepine dihydrate (CBD). Accordingly, formulation of sustained release products of CBZ is a promising approach to overcome this problem. Microsponges is an emerging formulation which can help in this direction. The aim of this work was to optimize the composition of microsponges for better encapsulation and sustained release of CBZ for oral administration. CBZ microsponges were prepared using quasi emulsion solvent diffusion technique with varying composition of ethyl cellulose and polyvinyl alcohol (PVA). Microsponges were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction. Production yield, entrapment efficiency and surface morphology of microsponges were assessed in addition to drug release. Optimum formulation was administered orally to albino rabbits to evaluate the oral bioavailability with reference to unprocessed CBZ. The Instrumental analysis reflected the encapsulation of CBZ in amorphous or molecularly dispersed form in the microsponges. The size and entrapment efficiency of the microsponges increased with increasing polymer contents. This was associated with reduction in CBZ release. Optimum formulation enhanced the oral absorption of CBZ. This was manifested by 2.6-fold increase in the area under the plasma concentration versus time curve compared to that of unprocessed CBZ. The study introduced microsponges as promising carriers for sustained oral delivery of CBZ.

scholarly journals Self Emulsifying Drug Delivery System: A Recent Approach

2019 ◽  
Vol 31 (4) ◽  
pp. 751-759 ◽  
Author(s):  
Sabitri Bindhani ◽  
S. Mohapatra ◽  
R.K. Kar
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Bioavailability ◽  
Oral Absorption ◽  
Scale Up ◽  
Aqueous Solubility ◽  
Oral Drug ◽  
Recent Approach ◽  
Poorly Soluble

In recent years, nearly 40 % newer drugs compounds are hydrophobic in nature, which is a major challenge now-a-days for oral drug delivering due to low aqueous solubility. Lipid based drug delivery system is one of the favourable approach for poorly soluble compounds which can improve the drug absorption and oral bioavailability. Due to ion-pairing with appropriate surfactant and co-surfactant the macromolecular drug molecular oil droplet being found in the gut flow oral absorption which sufficiently stable towards lipase. Due to the formation of emulsified drug in micron level, it can efficiently endow the oral bioavailability. Several comprehensive papers have been published in the literature illustration diverse type of lipid based formulation with recent advancements. This article is based on an exhaustive and updated review on newer technology which out line an explicit discussion on its formulations and industrial scale up.

Nanonization of andrographolide by a wet milling method: the effects of vitamin E TPGS and oral bioavailability enhancement

RSC Advances ◽  
2016 ◽  
Vol 6 (103) ◽  
pp. 101404-101414 ◽  
Author(s):  
Ping Du ◽  
Qikun Jiang ◽  
Rujie Yang ◽  
Cuiru Liu ◽  
Yingchao Li ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Clinical Use ◽  
Wet Milling ◽  
Bioavailability Enhancement ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Vitamin E Tpgs ◽  
Extensive Metabolism ◽  
Milling Method ◽  
Low Solubility

Andrographolide (AND) has wide prospects in clinical use, but suffers from the restriction of poor oral bioavailability, due to its low solubility, rapid and extensive metabolism and efflux by P-glycoprotein (P-gp).

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