Skin Penetrating Peptide as a Tool to Enhance the Permeation of Heparin through Human Epidermis.

This study aimed to identify a new skin penetrating peptide (SPP) able to enhance unfractionated heparin (UFH) permeation through human epidermis by screening a phage display peptide library. The effects of the synthesized heptapeptide (DRTTLTN) on human stratum corneum organization were investigated by ATR-FTIR spectroscopy and molecular dynamics simulation. The DRTTLTN penetration within the human epidermis caused both a fluidization of the stratum corneum lipids and the extension of keratins due to the increase of the contribution of α-helices.

Application of methyl methacrylate copolymers to the development of transdermal or loco-regional drug delivery systems.

Introduction: Methyl methacrylate copolymers (Eudragit®) have been exploited to develop transdermal patches, medicated plasters (hereinafter patches) and, more recently, film-forming sprays, microsponges and nanoparticles intended to be applied on the skin.

Areas Covered: The article reviews the information regarding the application of Eudragits in the design and development of these dosage forms focusing on the impact of formulative variables on the skin drug penetration and the patch adhesive properties.

Expert Opinion: Eudragits combined with a large amount of plasticizers are used to design the pressure-sensitive adhesives, specialized materials used in the patch development.

Formulation study of a patch containing propranolol by design of experiments.

Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR).

Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2(4) full factorial design. The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane.

An investigation into silk fibroin conformation in composite materials intended for drug delivery.

Regenerated silk fibroin (SF) is a promising biomaterial to design drug delivery systems. To guarantee satisfactory prolonged release of loaded drugs, the native β-sheet conformation of SF is generally induced by a final curing which can determine instability of the loaded drug. This work aimed to investigate the influence on SF conformation of the addition of hydrophilic polymers, namely poloxamer 188 (PEO), a range of poly(ethylenglycol) (PEG)and poly(vinyl pyrrolidone) (PVP) and drying conditions, namely spray-drying or evaporation at 60 °C.

Injectability evaluation: an open issue.

The current work aimed to propose a system of scoring to rationalize and support the selection of the optimal diameter and length of needles. Four formulations at different viscosity and needles ranging from 21 to 26 G and length ranging from 16 to 40 mm were used. Plunger-stopper breakloose force, maximum force (F(max)), and dynamic glide force were measured by a texture analyzer at the crosshead speed of 1 mm/s.

Nicotine fast dissolving films made of maltodextrins: a feasibility study.

This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film tensile properties.

Diclofenac fast-dissolving film: suppression of bitterness by a taste-sensing system.

Context: The selection of a proper taste-masking agent (TMA) is a critical issue in the development of fast-dissolving films containing bitter drugs.

Objective: This work is aimed to evaluate the suppression of the bitter taste of a maltodextrin fast-dissolving film loaded with 13.4 mg sodium diclofenac (DS) by adding TMAs.

A novel polymethylmethacrylate hydrophilic adhesive matrix intended for transdermal patch formulations.

A novel poly(sodium methacrylate, methylmethacrylate) hydrophilic pressure sensitive adhesive (PSA) containing a large amount of water was designed. The effects of PEG400, glycerin, sorbitol, and/or NaCl on the in vitro and in vivo adhesive properties were investigated by means of a 2(4) full factorial design. The optimized formulation, containing all independent variables at the highest value, was loaded with lidocaine hydrochloride (LH).

The effects of excipients for topical preparations on the human skin permeability of terpinen-4-ol contained in Tea tree oil: infrared spectroscopic investigations.

This work aimed to evaluate the effect induced by excipients conventionally used for topical dosage forms, namely isopropyl myristate (IPM) or oleic acid (OA) or polyethylene glycol 400 (PEG400) or Transcutol (TR), on the human skin permeability of terpinen-4-ol (T4OL) contained in the pure Tea tree oil. The effect of such excipients was determined by evaluating the absorption of T4OL using human epidermis and the perturbation of the organization of stratum corneum by ATR-FTIR. Among the tested excipients OA enhanced the absorption of T4OL by perturbing the stratum corneum lipid barrier.

Sculptured drug-eluting stent for the on-site delivery of tacrolimus.

This work aimed to evaluate the flexibility of a novel pyrolytic carbon coated drug-eluting stent platform, which presents the peculiarity of deep sculptures realized on the stent's outer surface (reservoirs). Tacrolimus (TCR) or TCR/excipient mixtures were loaded into the reservoirs, and their permanence into stent's reservoirs was verified by an in vitro short-time release test in human blood. Moreover, the impact of the excipients on the TCR physical state and surface morphology of the reservoirs and the release kinetics were studied.

An investigation into the influence of counterion on the RS-propranolol and S-propranolol skin permeability.

The effects of two contra-ions, namely benzoate (Bz) and oleate (Ol), on the in vitro human skin permeability of propranolol racemate (RS-PR) or S-enantiomer (S-PR) were studied. Saline solution (SS) or mineral oil (MO) were selected as vehicles. The MO increased the permeability coefficient (K(p)) of PR-Bz (pK(p) approximately 4) of about four times with respect to SS (pK(p) approximately 8) probably due to the ion pair formation.

Formulation study of tea tree oil patches.

The antimicrobial, antifungal and anti-inflammatory properties of tea tree oil (TTO), the essential oil of Melaleuca alternifolia are well documented. In order to optimize its therapeutic activity, TTO patches were designed. The aim of this work was the formulation of monolayer patches containing TTO.

Design of methylprednisolone biodegradable microspheres intended for intra-articular administration.

This study aimed to design methyprednisolone (MP)-loaded poly(D,L lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different types of PLGA by using an S/O/W technique. The effects of beta-irradiation at the dose of 25 kGy were evaluated on the chemical and physicochemical properties of MS and the drug release profiles.

Fast dissolving films made of maltodextrins.

This work aimed to study maltodextrins (MDX) with a low dextrose equivalent as film forming material and their application in the design of oral fast-dissolving films. The suitable plasticizer and its concentration were selected on the basis of flexibility, tensile strength and stickiness of MDX films, and the MDX/plasticizer interactions were investigated by ATR-FTIR spectroscopy. Flexible films were obtained by using 16-20% w/w glycerin (GLY).

Design and characterization of an adhesive matrix based on a poly(ethyl acrylate, methyl methacrylate).

The main issue in the development of transdermal patches made of poly(ethyl acrylate, methyl methacrylate) (Eudragit NE 40D, PMM) is the shrinkage phenomenon during the spreading of the latex onto the release liner. To solve this problem, the latex is usually freeze-dried and then re-dissolved in an organic solvent (method 1). To simplify the production process, we prepared an adhesive matrix by adding to the commercial PMM latex a plasticizer and an additive (anti-shrinkage agent) that avoids the shrinkage of the water dispersion spread onto the release liner (method 2).

Evaluation of the topical anti-inflammatory activity of ginger dry extracts from solutions and plasters.

In this study the skin permeation and the topical anti-inflammatory properties of ginger extracts were investigated. A commercial ginger dry extract (DE) and a gingerols-enriched dry extract (EDE) were evaluated for their in vivo topical anti-inflammatory activity by inhibition of Croton oil-induced ear oedema in mice. Furthermore, the feasibility of an anti-inflammatory plaster containing DE or EDE was evaluated.

Characterization and physical stability of fast-dissolving microparticles containing nifedipine.

The suitability of a poly(sodium methacrylate, methyl methacrylate) (NaPMM), a novel mucoadhesive material, to prepare fast-dissolving microparticles containing nifedipine (NIF) in the range of 25-75% w/w was verified. Microparticles made of a low-viscosity hydroxypropylmethylcellulose (HPMC), were also prepared to compare the NIF release profile and bioadhesive properties. The release test was carried out in oversaturation conditions.

Formulation study of oxybutynin patches.

The present feasibility study was designed to obtain a monolayer patch containing oxybutynin (OXY) avoiding chemical permeation enhancers. The highest flux was obtained with a polydimethylsiloxane matrix patch. Because OXY crystals were detected in the matrix within a week, two amino methylmethacrylate copolymers (Eudragit E or Eudragit RS) were used as OXY crystallization inhibitors.

Binary polymeric blends to microencapsulate nitroflurbiprofen: physicochemical and in silico studies.

Nitroflurbiprofen, NFP, a practically insoluble liquid drug, was microencapsulated in hydrophilic micromatrices made of poly(N-vinylpyrrolidone) (PVP), or polyaminomethacrylate (PAMA), or binary blends of polymers thereof. The PAMA/PVP miscibility was assessed both in the solid state (DSC and ATF-FTIR spectroscopy) and in solution by viscometric measurements. The in vitro NFP release test was carried out in over saturation condition to discriminate the increase of NFP apparent solubility (supersaturation degree, SD).

Semisolid formulations containing dimethyl sulfoxide and alpha-tocopherol for the treatment of extravasation of antiblastic agents.

The topical treatment with dimethyl sulfoxide (DMSO) and/or alpha-tocopherol (alpha-T) is widely used in order to prevent the local complications of extravasation of cytostatic drugs and protect patients against skin ulceration. Till now, DMSO and alpha-T have been mainly used in solution. The goal of this study was to formulate semisolid preparations for cutaneous application differing in the hydrophilic and lipophilic properties and containing DMSO and alpha-T in combination.

Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles.

The ex vivo permeation of diclofenac was studied using four different salts (sodium, potassium, diethylamine, and epolamine) dissolved in four different solvents (water, propylene glycol (PG), Transcutol, and oleic acid (OA)) as donor phases through a human skin membrane. The four salts show different solubility values and different behavior in the four solvents, which are also permeation enhancers and this fact further is connected to the permeation results. The same order of magnitude of fluxes through the membrane as those previously reported for acidic diclofenac released from buffer solutions of pH >7 were found, taking into account differences originated by different membranes and other parameters tested in the experiments.

Evaluation of ex vivo human skin permeation of genistein and daidzein.

The percutaneous absorption of genistein (GEN) and daidzein (DAI), whose oestrogenic-like activity is well known, is scantily investigated. In this work the ability of GEN and DAI to reach therapeutic steady-state plasma concentrations following transdermal administration was studied. The skin permeation studies were conducted by using modified Franz diffusion cell and human epidermis as a membrane.

Comparison between gamma and beta irradiation effects on hydroxypropylmethylcellulose and gelatin hard capsules.

The effects of electron beam or gamma-irradiation on technological performances (capsule hardness, expressed as deforming work and dissolution time) of empty 2-shell capsules made of gelatin or hydroxypropylmethylcellulose (HPMC) were studied. Capsule structural changes induced by radiation treatment were investigated by capillary viscometry and atomic force microscopy (AFM). The capsules were irradiated in the air at 5, 15, and 25 kGy.

The effects of bivalent inorganic salts on the mucoadhesive performance of a polymethylmethacrylate sodium salt.

The effects of bivalent inorganic salts, namely CaCl2, MgCl2, MgSO4, ZnCl2 and ZnSO4, on the mucoadhesive performance of a polymethylmethacrylate sodium salt (EuSNa) were investigated. The swelling properties and mucoadhesion of ten different blends made of EuSNa and 5 or 10% (m/m) inorganic salts were evaluated. Only the addition of Zn salts caused a significant reduction of mucoadhesive properties and an increase of swelling.