Microneedle/nanoencapsulation-mediated transdermal delivery: mechanistic insights.

A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array. Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes.

Effect of microneedle treatment on the skin permeation of a nanoencapsulated dye.

Objectives: The aim of the study was to investigate the effect of microneedle (MN) pretreatment on the transdermal delivery of a model drug (Rhodamine B, Rh B) encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) focusing on the MN characteristics and application variables.

Methods: Gantrez MNs were fabricated using laser-engineered silicone micro-mould templates. PLGA NPs were prepared using a modified emulsion-diffusion-evaporation method and characterised in vitro.

Flux of ionic dyes across microneedle-treated skin: effect of molecular characteristics.

Drug flux across microneedle (MN)-treated skin is influenced by the characteristics of the MN array, formed microconduits and physicochemical properties of the drug molecules in addition to the overall diffusional resistance of microconduits and viable tissue. Relative implication of these factors has not been fully explored. In the present study, the in vitro permeation of a series of six structurally related ionic xanthene dyes with different molecular weights (MW) and chemical substituents, across polymer MN-pretreated porcine skin was investigated in relation of their molecular characteristics.

Laser-engineered dissolving microneedles for active transdermal delivery of nadroparin calcium.

There is an urgent need to replace the injection currently used for low molecular weight heparin (LMWH) multidose therapy with a non- or minimally invasive delivery approach. In this study, laser-engineered dissolving microneedle (DMN) arrays fabricated from aqueous blends of 15% w/w poly(methylvinylether-co-maleic anhydride) were used for the first time in active transdermal delivery of the LMWH nadroparin calcium (NC). Importantly, an array loading of 630IU of NC was achieved without compromising the array mechanical strength or drug bioactivity.

Lyophilized inserts for nasal administration harboring bacteriophage selective for Staphylococcus aureus: in vitro evaluation.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) poses an infection risk and eradication during hospitalization is recommended. Bacteriophage therapy may be effective in this scenario but suitable nasal formulations have yet to be developed. Here we show that lyophilization of bacteriophages in 1ml of a viscous solution of 1-2% (w/v) hydroxypropyl methylcellulose (HPMC) with/without the addition of 1% (w/v) mannitol, contained in Eppendorf tubes, yields nasal inserts composed of a highly porous leaflet-like matrix.

Correlation between in vitro and in vivo erosion behaviour of erodible tablets using gamma scintigraphy.

In vitro and in vivo erosion behaviour of erodible tablets consisting of glyceryl behenate and low-substituted hydroxypropylcellulose manufactured using three different methods: direct compression (DC), melt granulation (MG) and direct solidification (DS) was investigated. In vitro erosion behaviour was studied using gravimetric and scintigraphic methods. For scintigraphic investigations, the radiolabel was adsorbed onto activated charcoal and incorporated into tablets at a concentration that did not affect the erosion profile.

Synthesis, processing and solid state excipient interactions of cucurbit[6]uril and its formulation into tablets for oral drug delivery.

The synthesis, processing, and solid state excipient interactions of cucurbit[6]uril (CB[6]) and its formulation into oral tablets has been examined using a range of physical chemistry techniques. Rapid precipitation from HCl by the addition of water yields microcrystalline CB[6] with smaller and more consistent particle size (30-165 μm) compared with the sieved CB[6] (50-540 μm) produced from large crystals grown by slow evaporation from HCl. The microcrystalline particles also contain fewer water molecules in the crystal compared with the sieved particles: 10 and 16% respectively.

In-vitro and in-vivo erosion profiles of hydroxypropylmethylcellulose (HPMC) matrix tablets.

The purpose of this study was to evaluate and compare the in-vitro and in-vivo erosion profiles of two tablet formulations primarily consisting of hydroxypropylmethylcellulose (HPMC) and lactose. HPMC was used at concentrations below and above the reported values for polymer percolation threshold in controlled release matrix formulations: 20 and 40% (w/w) HPMC. In-vitro erosion behaviour was studied using traditional gravimetric and scintigraphic methods, with radiolabelled charcoal used as a marker to quantify erosion profiles in scintigraphic studies.

Solid state stabilisation of the orally delivered drugs atenolol, glibenclamide, memantine and paracetamol through their complexation with cucurbit[7]uril.

The inclusion of the cardiovascular beta-blocker drug atenolol, the antidiabetic drug glibenclamide, the Alzheimer's NMDA glutamate receptor drug memantine and the analgesic/antipyretic drug paracetamol by cucurbit[7]uril (CB[7]) has been studied by (1)H nuclear magnetic resonance spectroscopy, electrospray ionisation mass spectrometry, molecular modelling, fluorescence displacement assays and differential scanning calorimetry. All four drugs form 1 : 1 host-guest complexes with CB[7], but the exchange kinetics and location of the binding is different for each drug. Atenolol is bound over the central phenyl ring with a binding constant of 4.

A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery.

Single crystal and powder X-ray diffraction have been used to examine the host-guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH(3))(2)}(2)mu-dpzm](2+) (di-Pt, dpzm= 4,4'-dipyrazolylmethane). The single crystal structure shows that the host-guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls.

In vivo performance of an oral MR matrix tablet formulation in the beagle dog in the fed and fasted state: assessment of mechanical weakness.

Purpose: To evaluate the behaviour of an oral matrix modified release formulation in the canine gastrointestinal tract, and establish if a mechanical weakness previously observed in clinical studies would have been identified in the dog model.

Materials And Methods: In vitro release profiles were obtained for two modified release matrix tablets containing UK-294,315, designed to release over either 6 (formulation A) or 18 (formulation B) hours. Tablets were labelled with (153)samarium and in vivo pharmacoscintigraphy studies were performed in four beagle dogs in the fasted state for both formulations, and following ingestion of an FDA high fat meal for formulation B.

Evaluation of the clearance of a sublingual buprenorphine spray in the beagle dog using gamma scintigraphy.

Purpose: The aim of this study was to evaluate clearance from the buccal cavity and pharmacokinetic profiles of a sublingual spray formulation in the dog, to assist in interpretation of future pharmacokinetic studies.

Methods: Radiolabelled buprenorphine in a spray formulation (400 microg/100 microl in 30% ethanol) was administered sublingually to four beagle dogs, and the residence in the oral cavity was determined using gamma scintigraphy. Pharmacokinetic sampling was performed to facilitate correlation of location of dose with significant pharmacokinetic events.

The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulations.

A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration.

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state.

Nasal residence of insulin containing lyophilised nasal insert formulations, using gamma scintigraphy.

Bioadhesive dosage forms are a potential method for overcoming rapid mucociliary transport in the nose. A lyophilised nasal insert formulation previously investigated in sheep demonstrated prolonged absorption of nicotine hydrogen tartrate suggestive of extended nasal residence, and increased bioavailability. The current study was performed to quantify nasal residence of the formulations using gamma scintigraphy, and to investigate the absorption of a larger molecule, namely insulin.

The Effect of Preoperative Aspirin and/or Heparin Therapy on Coagulation and Postoperative Blood Loss after Coronary Artery Bypass Surgery.

Objective: To assess the effects of preoperative aspirin and/or intravenous heparin therapy on perioperative coagulation tests and postoperative blood loss for 24-hour after coronary artery bypass surgery.

Methods: Multiple conventional coagulation tests, activated clotting time, thrombelastograph, skin bleeding time and platelet aggregation were performed before induction of anaesthesia, following protamine administration and after skin closure in 45 patients.

Results: There was no significant difference in either coagulation tests or postoperative blood loss (median of 860 mL with a range of 275 to 2800 mL, versus 833 ml with a range of 500-1380 mL) between the aspirin and no-aspirin patients.

In vivo evaluation of nicotine lyophilised nasal insert in sheep.

The nasal route offers an attractive means of delivering a drug directly to the systemic circulation and avoiding hepatic first-pass metabolism, although rapid mucociliary clearance can be detrimental to nasal absorption. The in vitro and in vivo characteristics of a nasal insert formulation prepared by lyophilisation of a viscous HPMC gel solution designed to overcome this problem were studied. In vitro release of nicotine from the lyophilised insert was compared with powder and spray formulations.

On the influence of laryngeal pathologies on acoustic and electroglottographic jitter measures.

This study compared acoustic and electroglottographic (EGG) jitter from [a] vowels of 103 dysphonic speakers. The EGG recordings were chosen according to their intensity, signal-to-noise ratio, and percentage of unvoiced intervals, while acoustic signals were selected based on voicing detection and the reliability of jitter extraction. The agreement between jitter measures was expressed numerically as a normalized difference.

Prediction of the mediastinal drainage after coronary artery bypass surgery.

Using multiple correlation and linear regression approaches, we investigated the association between the amount of mediastinal drainage for the first 24 postoperative hours and clinical variables as well as multiple haematological tests performed at three time points: before anaesthesia induction, 10 minutes after protamine administration and just after skin closure, on 46 patients undergoing primary coronary artery bypass grafting. Three models from the three times were then developed to predict mediastinal drainage. The number of internal mammary grafts, the total number of grafts and plasma fibrinogen concentration were useful predictors of mediastinal drainage at all three times.

Comparative assessment of electroglottographic and acoustic measures of jitter in pathological voices.

Jitter, or the amount of cycle-to-cycle variation in the fundamental frequency, is a characteristic of the vocal folds' vibration that may affect electroglottographic (EGG) and acoustic signals in similar ways, because the translaryngeal conductance and the oral pressure are modulated by the same physiological mechanism. Despite the apparent simplicity in jitter computation and the relative facility in recording and analyzing EGG signals, only a few studies comparing EGG and acoustic jitter have been reported. This can be attributed to the remarkable sensitivity of measures of acoustic jitter to such features as the type of sound being analyzed, the equipment used for data acquisition, or the algorithms used to identify glottal cycle boundaries.