Biorelevant release testing of biodegradable microspheres intended for intra-articular administration

Characterization of controlled release formulations used for intra-articular (IA) drug administration is challenging. Bio-relevant synovial fluids (BSF), containing physiologically relevant amounts of hyaluronic acid, phospholipids and proteins, were recently proposed to simulate healthy and osteoarthritic conditions. This work aims to evaluate the performance of different controlled release formulations of methylprednisolone (MP) for IA administration, under healthy and disease states simulated conditions. Microspheres differed in grade of poly(lactide-co-glycolide) and in the theoretical drug content (i.e. 23 or 30% w/w). Their performance was compared with the commercially available suspension of MP acetate (MPA). Under osteoarthritic state simulated condition, proteins increased the MPA release and reduced the MPA hydrolysis rate, over 48\u202fh. Regarding microspheres, the release patterns over 40 days were significantly influenced by the composition of BSF. The pattern of the release mechanism and the amount released was affected by the presence of proteins. Protein concentration affected the release and the concentration used is critical, particularly given the relevance of the concentrations to target patient populations, i.e. patients with osteoarthritis

Regenerated keratin membrane to match the in vitro drug diffusion through human epidermis

AbstractThis work aimed to develop membranes made of regenerated keratin and ceramides (CERs) to match the barrier property of the human stratum corneum in in vitro percutaneous absorption studies. The membrane composition was optimized on the basis of the in vitro drug diffusion profiles of ibuprofen, propranolol and testosterone chosen as model drugs on the basis of their different diffusion and solubility properties. The data were compared to those obtained using human epidermis.The ATR-FTIR and SEM analyses revealed that CERs were suspended into the regenerated keratin matrix, even if a partial solubilization occurred. It resulted in the membranes being physically stable after exposure to aqueous buffer and/or mineral oil and the fluxes of ibuprofen and propranolol from these vehicles through membranes and human skin were of the same order of magnitude. The best relationship with human epidermis data was obtained with 180μm-thick membrane containing 1% ceramide III and 1% ceramide VI. The data on the testosterone diffusion were affected by the exposure of the membrane to a water/ethanol solution over a prolonged period of time, indicating that such an organic solvent was able to modify the supermolecular organization of keratin and CERs.The keratin/CER membranes can represent a simplified model to assay the in vitro skin permeability study of small molecules

A controlled, randomized clinical study to verify the efficacy and safety of a new hypertonic solution (Narlisim) in nasal congestion in adults affected by common cold

Background: Nasal congestion is the main symptom of common cold. Symptomatic treatment with nasal decongestant seems to be the only treatment option. We managed a study to assess the efficacy of Narlisim, a developed nasal spray, on nasal congestions in common cold. Materials and methods: In this study, sixty adult patients with common cold were included. Thirty patients were treated with Narlisim nasal spray, and 30 patients with isotonic nasal spray. The primary outcome was the assessment of the speed of relief of nasal congestion; the secondary outcome was the assessment of nasal congestion and nasal secretion symptoms by a 0–100% rating Visual analog score (VAS) scale on 5 items at baseline and after 5, 10, 15, 20, 25 and 30 minutes from treatment. Results: VAS score progressively reduced for all investigated symptoms in both groups; a statistically significant higher mean reduction at each time point was recorded in the study group compared to controls (p<0.001). Conclusions: Our results suggest that Narlisim may be a promising medical device to control nasal congestion and rhinitis in common cold thanks to its nasal washing, hypertonic city, and low pH and osmo protection properties

Preformulation and formulation studies of dermal patches based on methacrylic matrices

Dottorato di ricerca in tecnologia e legislazione del farmaco e delle molecole bioattive. 12. ciclo. A.a. 1996-99. Coordinatore G. Podda. Tutore L. MontanariConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Spotlight on Calcipotriol/Betamethasone Fixed-Dose Combination in Topical Formulations: Is There Still Room for Innovation?

Psoriasis is a lifelong disease which requires treatment adherence for successful management. Considering the complexity of this pathology, the combination of active pharmaceutical ingredients with a synergistic mechanism of action can improve the safety and efficacy of the treatment with respect to the conventional monotherapy. Moreover, a fixed dose of therapeutic agents in a topical formulation offers the possibility to simplify administration, reduce the doses of each active ingredient, and improve patient&rsquo;s compliance. Among the first-line treatments in mild to moderate psoriasis, the formulation of calcipotriol (Cal) and betamethasone dipropionate (BD) in a single vehicle is challenging due to their chemical incompatibility in an aqueous environment and the formation of degradation products. Based on these considerations, this review aims to provide an overview on the biopharmaceutical properties of Cal/BD fixed-dose combination products available on the market (namely ointment, oleogel, foam, and O/W cream), highlighting also the novel approaches under evaluation. The main differences among topical formulations are discussed considering the different features of the anatomic districts involved in psoriasis and the patient&rsquo;s adherence. Moreover, since in vitro experiments are fundamental to evaluate the skin permeation profile during the development of an efficacious medicinal product, special emphasis is given to models proposed to mimic psoriatic lesions

Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA) to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA) was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C). By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE), suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%). Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs

Alternatives When an Authorized Medicinal Product is Not Available

The industrialization of medicinal products has permitted us to reach important results in terms of quality, efficacy, safety, and availability of drugs; however, not all the legitimate expectations of patients are met. When an authorized medicinal product is not available on the market, the physician can prescribe other pharmacological treatments in the following scenario: off-label prescriptions, extemporaneous preparations, compassionate use of medicinal products, and medicinal products authorized in foreign countries. The best solution among these alternatives should be evaluated case-by-case on the basis of good scientific evidence, expert medical judgement, and published literature, also keeping an eye on the availability, the cost, and the regulatory requirements at a national level

Echinacea angustifolia DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies

Dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) is the main component of Echinacea angustifolia DC. lipophilic extract, the bioavailability and immunomodulatory eect after oral administration in soft gel capsules in healthy volunteers of whichwehave already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide. The first step, therefore, encompassed the preparation of a drug-in-adhesive patch with an area of 868 mm2 and containing a dose of 0.64 mg of tetraene. In vitro skin permeation studies in Franz-type diusion chambers resulted in a tetraene flux of (103 10) ng cm2 h1 with a very good linearity (r = 0.99). The relatively low lag time of just 13 min indicates low binding and the accumulation of tetraene in the skin. Finally, the patch was administered to six healthy volunteers, and the pharmacokinetic analysis was performed by nonlinear mixed eects modelling with soft gel oral capsules serving as the reference formulation. The in vivo results correlated well with the in vitro permeation and indicated an initial burst tetraene absorption from the patch that was in parallel with the zero-order kinetics of absorption. The rate of the latter process was in good agreement with the one estimated in vitro. The tetraene absorption rate was therefore slow and prolonged with time, resulting in a bioavailability of 39% relative to the soft gel capsules and a very flat plasma concentration profile