Collaborative permeation of drug and excipients in transdermal formulations. In vitro scrutiny for ethanol:limonene combinations.

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance. Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them.

In vivo pharmacokinetic evaluation of carprofen delivery from intra-articular nanoparticles in rabbits: A population modelling approach.

Osteoarthritis is treated with COX or fosfolipase A2 inhibitors such as carprofen, a propionic acid NSAID. The enhancement of its action over the articular cartilage is mandatory to facilitate its therapeutic application. Drug uptake into the cartilage requires high synovial fluid concentrations, anticipating its rapid distribution towards bloodstream. Thus, intraarticular administration improves local targeting of the drug, lining with the site of action. A pharmacokinetic study in rabbits has been performed to evaluate carprofen nanoparticles after intraarticular administration. Pharmacokinetic analysis of plasma profiles through a modelling approach, has demonstrated the rapid distribution of drug outside of synovial chamber but mainly remaining in plasma. The data modelling has demonstrated the existence of two release-absorption processes when the nanoparticles are administered in the synovial space. Additionally, results are predictive of the PK profile of some other species such as cat, dogs or humans.

Remote pharmaceutical care for patients with rheumatoid arthritis and psoriasis.

BackgroundAccess to drugs with hospital-restricted dispensation, such as those for patients with rheumatoid arthritis or psoriasis, is regulated by healthcare policy. These drugs have the greatest cost-effective impact on the healthcare system. This is why a model for Pharmaceutical Care based on follow-up teleconsultations was defined in our hospital to improve patient well-being. Objective To evaluate clinical changes on patients when our remote Pharmaceutical Care model is applied and describe the work carried out by pharmacists when applying it. Setting Pharmacy Department of a Hospital in Barcelona, Spain. Method Cross-sectional observational study of the remote Pharmaceutical Care model developed by Clinical Pharmacists. All patients diagnosed with psoriasis or rheumatoid arthritis who were receiving active treatment with Hospital/Specialist only drugs, during the period from May to December 2018, were included. Main outcome measures The corresponding healthcare activity was recorded and to determine the utility of the model, the clinical response to treatment of patients included in the study was recorded. Results The implementation of teleconsultation is statistically related to the biological treatment response of patients with psoriasis (p = 0.006) and rheumatoid arthritis (p = 0.019). In those patients the healthcare activity of calculating and/or recording clinical variables of effectiveness/safety is statistically associated to biological treatment response (65.62% vs 35%, p = 0.015 and 73.14% vs 53.26%, p = 0.003). Conclusions The implementation of the model described lends added value to traditional pharmacotherapeutic management of biological treatments in patients with rheumatoid arthritis and psoriasis since response is improved but patient well-being is not diminished.

Pranoprofen quantification in ex vivo corneal and scleral permeation samples: Analytical validation.

The investigation of the ocular permeability and/or distribution of pranoprofen (PF), a non-steroidal antiinflamatory drug, demands for the selective analysis of its transit through specific ocular membranes. Therefore, customised ex vivo permeation experiments through external ocular tissues (cornea and sclera) have been validated for this drug in addition to its HPLC-UV quantification following standard bioanalytical guidelines. Chromatographic conditions consist of an isocratic system to elute the drug with a C18 column with UV detection at 245 nm. Precision, expressed as the relative standard deviation (% RSD), ranged between 4.89 and 0.79% (intra-day) and between 9.02 and 2.14% (interday). Accuracy ranged between 5.15 and -1.92% in intra-day experiments and between 6.25 and -4.89% in inter-day experiments. Drug recovery from tissue samples was reproducible around 90% and considered satisfactory to adequately assess drug levels in target tissues. Results indicate that the procedure is valid for the quantitation of PF in those ophthalmic samples in the range of 6.5 µg/mL to 100 µg/ml. As a proof of concept, PF permeation profiles through porcine cornea and sclera with vertical diffusion cells have been generated and analyzed. Pilot experiments demonstrate its applicability to investigate permeation levels of PF from 22.31 µg/cm2 (about a 20% of the dose) until 500 µg/cm2 if required. Additionally, real tissue-retention samples were also generated to verify the goodness of this experimental setup.