Studies on solvent systems for enhanced skin permeation of venlafaxine hydrochloride

Venlafaxine hydrochloride (VH) is a serotonin-noradrenaline reuptake inhibitor indicated for treatment of depression disorder. It shows low biological half-life 5±2 h and low oral bioavailability 45±15 % due to extensive hepatic first-pass metabolism. Frequent administration of VH is required to maintain steady state plasma concentration of drug. To overcome hepatic first pass metabolism and to cross blood brain barrier for effectively achieving plasma concentration of VH in brain, we envisaged to develop transdermal drug delivery system containing VH loaded polymeric nanoparticles. Effect of solvent systems (SS), penetration enhancers (PE), and VH nanoparticles (VHNPs) on transdermal diffusion of drug were studied. VHNPs were prepared by double emulsion solvent evaporation method using high speed homogenizer followed by probe sonication. Poly (lactic-co-glycolic acid) and tween 80 were used as polymer and surfactant respectively. Mean particle size, polydispersity index, zeta potential, entrapment efficiency of optimized VHNPs were found to be 175.4 nm, 0.109, (-) 24 mV and 56 %.respectively. Scanning electron microscopy confirmed spherical shape of drug loaded polymeric nanoparticles. SS comprising 50% PG in EtOH shown maximum flux 158.67 ± 2.9 (µg/cm2/h) and lag time was found to be 5.60 ±0.16 h. The PE 5 (%v/v) limonene shown maximum flux 200.47±3.6 (µg/cm2/h) and lag time 3.17±0.11 h. The flux and lag time in case of VHNPs were found to be 192.24±3.20 (µg/cm2/h) and 4.22±0.14 h respectively. Based on flux, clearance and surface area of transdermal patch, a theoretical meaningful plasma level concentration of VH ranging from 12.85 to 128.5 (ng/mL) can be achieved. Keywords: Depression, Venlafaxine hydrochloride, Poly (lactic-co-glycolic acid), Solvent systems, Penetration enhancers, Nanoparticles (NPs)

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DESIGN AND CHARACTERIZATION OF NOVEL EMULGEL FOR PAIN MANAGEMENT

INDIAN DRUGS ◽

10.53879/id.53.10.10596 ◽

2016 ◽

Vol 53 (10) ◽

pp. 16-20

Author(s):

S. S Magdum ◽

◽

P.S Dounde ◽

D. D. Kamble ◽

S. V.* Patil ◽

...

Keyword(s):

Penetration Enhancers ◽

Gelling Agent ◽

Hydrophobic Drugs ◽

Hydrophilic Drugs ◽

First Pass Metabolism ◽

First Pass ◽

Formulation Parameters ◽

Gi Absorption ◽

Pass Metabolism

Topical DDS is a localized system preferred for drugs having hurdles like first pass metabolism through gastro intestinal absorption, reduced bioavailability, relatively short residence time and dose dumping. To provide continuous percutaneous absorption of drug at controlled rate which overcomes problems associated with GI absorption for oral DDS, semisolid formulations like cream, ointment and gel were preferred in topical DDS applied on skin. Amongst them gels having more aqueous portion have greater dissolution of drug. But these properties are suitable for hydrophilic drugs and not for hydrophobic drugs. This problem was solved by formulating an emulgel in which hydrophobic drugs can be incorporated in gel and used for topical application. The aim of this work was to develop emulgel of acelofenac a hydrophobic drug using Carbapol 940 as gelling agent and clove oil and mentha oil as penetration enhancers. Another aim was to investigate effect of concentration and formulation parameters on spreading coefficient drug release and viscosity of prepared emulgel.

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Polymeric nanoparticles loaded naringin and naringenin: effect of solvent, characterization, photodegradation and stability studies

Drug Analytical Research ◽

10.22456/2527-2616.108783 ◽

2020 ◽

Vol 4 (2) ◽

pp. 64-71

Author(s):

Leticia Malgarim Cordenonsi ◽

Rafaela Martins Sponchiado ◽

Jardel Rodrigo Bandeira ◽

Roberto Chris Vianna Santos ◽

Renata Platchek Raffin ◽

...

Keyword(s):

Polymeric Nanoparticles ◽

Degradation Study ◽

Minimal Inhibitory Concentrations ◽

Transmission Electron ◽

First Pass Metabolism ◽

First Pass ◽

Uv C ◽

Inflammatory Action ◽

Pass Metabolism

Naringin (NAR) and naringenin (NGE) are flavonoids with important effects, such as antioxidant, nephroprotective and anti-inflammatory action. However, factors such as poor solubility and oral bioavailability, gastrointestinal instability and extensive first pass metabolism lead to limited deliverability. As far as we know, there are no papers describing the use of combination of NAR and NGE in nanoparticles. This paper describes the development and characterization of new nanoparticles containing NAR and NGE (NAR-NGE-NPs) which were prepared by nanoprecipitation using ethanol or mixture of solvents. Size distribution of NAR-NGE-NPs demonstrated a narrow distribution (121 nm), low polydispersity (< 0.1), and encapsulation efficiencies were greater than 80%. Infrared spectroscopy analyses confirmed the structure of NAR-NGE-NPs and in transmission electron microscopy, NAR-NGE-NPs presented a spherical and regular shape. A degradation study by UV-C, NAR-NGE-NPs improved photostability and conferred protection against NAR and NGE degradation. Minimal inhibitory concentrations of NAR and NGE were evaluated, however samples did not show antimicrobial activity. In this investigation, new NAR-NGE-NPs were successfully developed by a nanoprecipitation technique, using Endragit®L100 as polymer and ethanol as solvent.

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Potential Nanospray Inhalation of Remdesivir and Hydroxychloroquine using Poly (lactic-co-glycolic) Acid as Fast Delivery for Covid-19 Treatment.

Journal of Pharmacy ◽

10.31436/jop.v1i1.50 ◽

2021 ◽

Vol 1 (1) ◽

pp. 34-44

Author(s):

Muhammad Taher ◽

Siti Syazwani Shaari ◽

Deny Susanti

Keyword(s):

Drug Delivery ◽

Glycolic Acid ◽

Review Article ◽

Converting Enzyme ◽

Dry Powder Inhalation ◽

First Pass Metabolism ◽

First Pass ◽

Site Of Action ◽

Alternative Delivery ◽

Pass Metabolism

Introduction: The oral medication of remdesivir and hydroxychloroquine face several limitations in covid-19 therapy. Despite having the first-pass metabolism, it also has a limitation in the patient who has hospitalised with a severe covid-19 infection. It is especially for a drug that is targeting the angiotensin-converting enzyme II (ACE2) receptor where the receptors are found abundantly in the lung, kidney, heart, and gastrointestinal tract. Therefore, an alternative delivery such as nanospray inhalation would provide a great benefit to those patients. Methods: Scientific sources from Scopus, PubMed, Google Scholar, EBSCO, ScienceDirect, and Elsevier were accessed for publication of this review article regarding the nanospray inhalation for Covid-19. Results: Since the main organ infected by SARS-CoV-2 is the esophagus and lung, inhalation may be the best route to deliver the drug to the site of action. It is proposed that poly (lactic-co-glycolic) acid to be used in the formulation. Conclusion: Poly (lactic-co-glycolic) acid (PLGA) is considered a suitable polymer since it is biocompatible and noncytotoxic, it is the most widely applied in drug delivery either as carrier or excipient for the optimal formulation and distribution of the drugs. Dry powder inhalation of remdesivir and hydroxychloroquine may be an alternative way to deliver the drug against Covid-19.

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Identification of a Cranberry Juice Product Capable of Inhibiting Enteric CYP3A-Mediated First-Pass Metabolism in Humans

Planta Medica ◽

10.1055/s-2008-1075176 ◽

2008 ◽

Vol 74 (03) ◽

Author(s):

N Ngo ◽

Z Yan ◽

TN Graf ◽

DR Carrizosa ◽

EC Dees ◽

...

Keyword(s):

Cranberry Juice ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

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Development, Characterization and Optimization of Mucoadhesive Tablet for Buccal Delivery of Domperidone

Drug Delivery Letters ◽

10.2174/2210303108666181108120840 ◽

2019 ◽

Vol 9 (1) ◽

pp. 37-49

Author(s):

Jagdale Sachin ◽

Panbude Aishwarya ◽

Navasare Priya

Keyword(s):

Drug Release ◽

Factorial Design ◽

Research Work ◽

Wet Granulation ◽

Buccal Delivery ◽

Scanning Calorimetry ◽

Mucoadhesive Polymers ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. </P><P> Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). </P><P> Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

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