<i>In-vitro</i> prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems

Wu, Zimei; Hassan, Dalia; Shaw, John

doi:10.1111/jphp.12114

Cited by 14 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis was confirmed by comparing the AIC for models B and C. Our study design cannot elucidate the physiological determinants of a zero-order absorption profile of the tested aqueous solutions of lidocaine hydrochloride, but such atypical absorption behavior may be associated with the lymphatic uptake of precipitated drug molecules [27], or their dissolution by the rate-limiting turnover of interstitial fluid, resulting in pseudo zero-order absorption [30]. Further research is needed to confirm this hypothesized mechanism for lidocaine hydrochloride [33]. …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs

et al. 2017

View full text Add to dashboard Cite

Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our objective was to develop a compartmental model for quantification of adrenaline’s impact on the pharmacokinetics of perineurally-injected lidocaine in the dog. Dogs were subjected to paravertebral brachial plexus block using lidocaine alone or adrenalinated lidocaine. Data was collected through a prospective, randomised, blinded crossover protocol performed over three periods. Blood samples were collected during 180 minutes following block execution. Compartmental pharmacokinetic models were developed and their goodness-of-fit were compared. The lowering effects of adrenaline on the absorption of lidocaine were statistically determined with one-sided tests. A one-compartment disposition model with two successive zero-order absorption processes best fitted our experimental data. Adrenaline decreased the peak plasma lidocaine concentration by approximately 60% (P < 0.001), decreased this local anesthetic’s fast and slow zero-order absorption rates respectively by 50% and 90% (P = 0.046, and P < 0.001), which respective durations were prolonged by 90% and 1300% (P < 0.020 and P < 0.001). Lidocaine demonstrated a previously unreported atypical absorption profile following its paravertebral injection in dogs. Adrenaline decreased the absorption rate of lidocaine and prolonged the duration of its absorption.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The latter aspect is important in subcutaneous drug delivery, where macromolecular drugs injected into the adipose tissue need to pass through the extracellular matrix in order to be absorbed by the circulatory system via blood capillaries or lymphatic vessels [ 31 , 32 , 33 , 34 , 35 ]. Experiments have shown that positively charged therapeutic proteins are absorbed at a lower rate than net negatively charged proteins.…”

Section: Introductionmentioning

confidence: 99%

Responsive Hyaluronic Acid–Ethylacrylamide Microgels Fabricated Using Microfluidics Technique

Wanselius

Rodler²,

Searle³

et al. 2022

Gels

View full text Add to dashboard Cite

Volume changes of responsive microgels can probe interactions between polyelectrolytes and species of opposite charges such as peptides and proteins. We have investigated a microfluidics method to synthesize highly responsive, covalently crosslinked, hyaluronic acid microgels for such purposes. Sodium hyaluronate (HA), pre-modified with ethylacrylamide functionalities, was crosslinked in aqueous droplets created with a microfluidic technique. We varied the microgel properties by changing the degree of modification and concentration of HA in the reaction mixture. The degree of modification was determined by 1H NMR. Light microscopy was used to investigate the responsiveness of the microgels to osmotic stress in aqueous saline solutions by simultaneously monitoring individual microgel species in hydrodynamic traps. The permeability of the microgels to FITC-dextrans of molecular weights between 4 and 250 kDa was investigated using confocal laser scanning microscopy. The results show that the microgels were spherical with diameters between 100 and 500 µm and the responsivity tunable by changing the degree of modification and the HA concentration. Microgels were fully permeable to all investigated FITC-dextran probes. The partitioning to the microgel from an aqueous solution decreased with the increasing molecular weight of the probe, which is in qualitative agreement with theories of homogeneous gel networks.

show abstract

“…Lipid-and oil-based drug delivery systems are widely used for increasing the solubility and bioavailability of hydrophobic drugs [1][2][3][4][5]. Various types of nanostructured lipid carriers, liquid crystalline lipid nanoparticles (cubosomes, spongosomes, hexosomes, liposomes), microemulsions, nanoemulsions, nanogels, solid lipid nanoparticles, and hybrid lipid-polymer nanoparticles have been investigated with the aim of encapsulation and protection of poor soluble or instable therapeutic molecules [6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

In situ phase transition of microemulsions for parenteral injection yielding lyotropic liquid crystalline carriers of the antitumor drug bufalin

Angelova

Liu

et al. 2019

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

In this work, we use the small angle X-ray scattering (SAXS) method for controlled preparation of in situ forming sustained-release carriers of the antitumor drug bufalin (BUF), which has very poor solubility and a considerable cardiotoxicity in a non-encapsulated state. To that aim, we exploit the pseudo-ternary phase diagram of an oil(O)/surfactant(S)/water(W) system containing medium chain capric/caprylic triglycerides (MCT) and a co-surfactant blend of Macrogol (15)-hydroxystearate (Solutol HS 15) and sorbitan monooleate (Span 80). Two compositions with different oil contents (B-LC-ME and C-LC-ME) are selected from the microemulsion region of the diagram in order to study the effect of the aqueous environment on their structural behaviour. A phase transition from a microemulsion to a lamellar liquid crystalline phase and multilamellar vesicles is established by SAXS upon progressive dilution. The drug bufalin (BUF) is encapsulated in the microemulsions, which have low viscosity, whereas the release of the drug occurred from the in situ generated lamellar liquid crystalline structures. The formulations are characterized by SAXS, dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM), rheology, drug loading and entrapment efficiency, and in vitro release profiles. A correlation is suggested between the structures of the in situ phase-transition formed LC-ME formulations and the differences in their viscosities and drug release profiles. The performed cytotoxicity, cell apoptosis and pharmacokinetic experiments show an enhanced bioavailability of BUF after encapsulation. These results suggest potential clinical applications for the obtained safe in situ phase-transition sustained-release formulations of BUF.

show abstract

In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems

Abstract: The in-vitro model can be used as a cost-effective screening tool in injectable formulation development for safe and effective delivery of poorly soluble drugs. PDP can be circumvented with a well-designed formulation.

Cited by 14 publications

References 46 publications

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs

Responsive Hyaluronic Acid–Ethylacrylamide Microgels Fabricated Using Microfluidics Technique

In situ phase transition of microemulsions for parenteral injection yielding lyotropic liquid crystalline carriers of the antitumor drug bufalin

Contact Info

Product

Resources

About