Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol

Lozoya-Agullo, Isabel; González‐Álvarez, Isabel; González‐Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

doi:10.1016/j.ejps.2016.08.035

Cited by 19 publications

(4 citation statements)

References 45 publications

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“…Our data demonstrate that the ion-pair approach improved the permeability of lisinopril ex-vivo. There are many studies claiming the improvement of permeability of active pharmaceutical ingredients through the ion-pair approach but most of them fail to achieve in-vivo efficacy [21]. For reason, we evaluated the effectiveness of optimized gel formulation by in-vivo studies.…”

Section: Discussionmentioning

confidence: 99%

QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits

PAWAR,

MORE,

BHATIA

2023

jrp

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Lisinopril belongs to BCS class III having high solubility and low permeability. Reportedly, the oral bioavailability of lisinopril is 25 to 30% and its effectiveness is limited due to poor permeability. Hence, the current investigation is aimed to formulate transdermal ion-pair gel using a permeation enhancer for enhanced delivery of lisinopril across the stratum corneum and evaluate pharmacokinetics of lisinopril in rabbits. The formation of ion-pair is corroborated using Fourier Transform Infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray Diffraction (XRD), zeta potential, particle size analysis, oil/water partition coefficient study, etc. Optimization of the formulation was done using 3 2 factorial designs. Total nine batches (F1-F9) were prepared and the effect of propylene glycol (mL; X1) and carbopol 934 (%; X2) was investigated on gel viscosity (Y1) and permeability through rabbit's skin at 8h (Y2). Propylene glycol exhibited a non-significant (p>0.05) effect on both gel viscosity and skin permeability whereas carbopol 934 demonstrated significant (p<0.05) positive and negative effects on both, respectively. The viscosity of all the lisinopril ion-pair gel (F1-F9) was ranging between 17.24 ± 2.16 Pa.s (Batch F9) to 7.54 ± 1.34 Pa.s (Batch F4). Ex-vivo permeability of all the prepared batches (F1-F9) across excised rabbit's skin was ranging between 85.93 ± 1.26% (Batch F4) to 62.17 ± 1.57% (Batch F9). Remarkably, optimized formulation (F4) exhibited 1.7 folds improvement in skin permeability and 2.4 folds improvement in bioavailability than plain lisinopril gel. These findings demonstrate that ion pair formation is a promising strategy for significantly improving the skin permeability of lisinopril.

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Section: Discussionmentioning

confidence: 99%

QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits

PAWAR,

MORE,

BHATIA

2023

jrp

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“…Thus, the development of oral dosage formulations and BA enhancement technology for candidate drugs seems to be at a critical stage [6]. However, there are many obstacles that may impede the development of oral dosage formulations, such as low intestinal solubility and permeability and the high intestinal first-pass effect [7][8][9]. Doxorubicin (DOX) (Figure 1), an anthracycline drug, is one of the most widely used chemotherapeutic drugs.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting

2023

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Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux. We reviewed various parenteral DOX formulations, such as liposomes, polymeric micelles, polymeric nanoparticles, and polymer-drug conjugates, under clinical use or trials to increase its therapeutic efficacy. To improve the bioavailability of DOX in intravenous and oral cancer treatment, studies have proposed a pH- or redox-sensitive and receptor-targeted system for overcoming DOX resistance and increasing therapeutic efficacy without causing DOX-induced toxicity. Multifunctional formulations of DOX with mucoadhesiveness and increased intestinal permeability through tight-junction modulation and P-gp inhibition have also been used as orally bioavailable DOX in the preclinical stage. The increasing trends of developing oral formulations from intravenous formulations, the application of mucoadhesive technology, permeation-enhancing technology, and pharmacokinetic modulation with functional excipients might facilitate the further development of oral DOX.

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“…At present, many Chinese medicinal components have been proved to have high activity in vitro experiments, but after oral administration, some Chinese medicinal active components, such as Panax noteginseng saponin have problems of poor intestinal absorption and low bioavailability, which affect the clinical e cacy and patients' medication compliance 6 . Therefore, it is particularly important to improve the intestinal absorption capacity and oral bioavailability of low permeability drugs 7 .…”

Section: Introductionmentioning

confidence: 99%

Oral absorption-promoting of Panax notoginseng saponins-loaded Nanoparticles modified with Thiolated trimethyl chitosan and Wheat germ agglutinin

Fang

Zhao

Lin

et al. 2023

Preprint

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Traditional Chinese medicine (TCM) oral preparations is the main means of disease treatment in TCM clinically, but the bioavailability of TCM active ingredients such as panax noteginseng saponins (PNS) is low due to its poor intestinal absorption. In this study, PNS nanoparticle modified with thiolated trimethyl chitosan (TMC-Cys) and wheat germ agglutinin (WGA) (PP-WT NPs) was prepared to promote the oral absorption of PNS effectively. In vitro studies demonstrated that PP-WT NPs delayed the release of PNS and had strong anti-enzyme activities against acids and digestive enzymes in the gastrointestinal environment. And it has good cell uptake and transport capacity in the Caco-2/HT29 co-cultured cell model. In vivo animal experiments showed that PP-WT NPs could penetrate the mucus layer barrier, and the effective permeability coefficients for R1, Rg1, and Rb1 in the small intestine were 1.68, 1.64, and 1.63 times than that of free PNS, respectively. It was predicted that panax notoginseng saponins-loaded nanoparticles modified with thiolated trimethyl chitosan and wheat germ agglutinin provide an attractive strategy for improving the oral absorption of PNS.

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Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol

Cited by 19 publications

References 45 publications

QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits

QbD-steered fabrication of lisinopril ion-pair gel for improved skin permeability and bioavailability in rabbits

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting

Oral absorption-promoting of Panax notoginseng saponins-loaded Nanoparticles modified with Thiolated trimethyl chitosan and Wheat germ agglutinin

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