ADHD Follow-Up in Adulthood among Subjects Treated for the Disorder in a Child and Adolescent Mental Health Service from 1995 to 2015

Background and Objectives: ADHD is a neurodevelopmental disorder characterized by inattention and hyperactivity/impulsivity and can persist in adulthood. The aim of this study is to deepen knowledge about adult ADHD follow-up. Materials and Methods: This observational study consists of one retrospective part aimed at collecting records of children and adolescents treated for ADHD in the Children and Adolescent Mental Health Service (CAMHS) from 1995 to 2015 and, successively, at identifying their adult follow-up in Adult Mental Health Service (AMHS); the second part consists of ADHD scale administration, Diagnostic Interview for ADHD in Adults (DIVA 2-0) and Adult Self Rating Scale (ASRSv1.1), for the subjects currently being treated at AMHS who agreed to participate in the study. Results: We observed that among the 55 patients treated at CAMHS between 1995 and 2015 for ADHD and subsequently at the AMHS, none presented a diagnosis of ADHD; instead, they were treated for Intellectual Dysfunction (33%), Borderline Personality Disorder (15%) and Anxiety Disorders (9%), and two individuals were also diagnosed with comorbid substance/alcohol abuse (4%). Of the 55 patients, only 25 (45%) were treated at AMHS during the study period. Though we asked for their informed consent to administer the questionnaires, we were able to test only seven patients. The ASRS-V1.1 score showed that 43% of patients reported symptoms of ADHD persistence in adulthood. For DIVA 2.0, 57% of individuals reported scores indicating the persistence of the ADHD inattention component, and 43% the persistence of both ADHD dimensions. Conclusions: ADHD cannot be considered a disorder confined to childhood/adolescence but instead is a chronic and complex condition that can persist into adulthood. The very small size of our final sample may account for both the high ADHD dropout rate over the long follow-up period and the difficult transition from child to adult health care in ADHD treatment. Our investigation suggests the need for specific training in the diagnosis and treatment of adult ADHD and the implementation of transition protocols between minor and adult services to improve long-term treatments

dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy

Abstract The purpose of this work was to study a new dry powder inhaler (DPI) of tobramycin capable to simplify the dose administration maneuvers to maximize the cystic fibrosis (CF) patient care in antibiotic inhalation therapy. For the purpose, tobramycin/sodium stearate powder (TobraPS) having a high drug content, was produced by spray drying, characterized and the aerodynamic behavior was investigated in vitro using different RS01 DPI inhalers. The aerosols produced with 28, 56 or 112 mg of tobramycin in TobraPS powder using capsules size #3, #2 or #0 showed that there was quasi linear relationship between the amount loaded in the device and the FPD. An in vivo study in healthy human volunteers showed that 3–6 inhalation acts were requested by the volunteers to inhale 120 mg of TobraPS powder loaded in a size #0 capsule aerosolized with a prototype RS01 device, according to their capability to inhale. The amount of powder emitted at 4 kPa pressure drop at constant air flow well correlated with the in vivo emission at dynamic flow, when the same volume of air passed through the device. The novel approach for the administration of 112 mg of tobramycin in one capsule could improve the convenience and adherence of the CF patient to the antibiotic therapy

Polymeric Films Loaded with Vitamin E and Aloe vera

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns

Agglomerati chimerici per la somministrazione extravascolare di farmaci

The applications of the powder agglomeration technology for an extra vascular administration were studied in this PhD thesis. This technology allowed to obtain soft agglomerates that are cluster of microparticles characterized by low crushing strength. Agglomeration of fine particles improve handling of bulk powders and produce better flowability. The structure and properties of agglomerates depend on the composition of microparticles. However, the main feature of agglomerates is the capability of recovering the size of the primary particles at the administration site by use of water. These peculiarities are suitable for the administration to children and/or elder people that presented swallowing problems. In particular, it was studied a mesalazine gastroresistant multiparticulate system, where the drug was entrapped in lipidic microcapsules. Then, they were agglomerated with excipient microparticles to increase the wettability of the system. Moreover, an extemporaneous formulation composed by artemisinin beta-cyclodextrin and clindamycin agglomerates for the treatment of the malaria was studied and characterized. Finally, a formulation of sodium levothyroxine agglomerates for buccal delivery system was studied since they were able to disintegrate in a minimum volume of liquid as the saliva.L'agglomerazione è un processo tecnologico che consente di modificare la dimensione delle microparticelle in modo reversibile. L’utilizzo di questa tecnologia permette di costruire particelle più grandi che siano in grado di ricreare le piccole solo nel sito di somministrazione. Gli agglomerati chimerici sono aggregati soffici di particelle più o meno piccole tenute insieme da deboli interazioni, tuttavia sufficientemente resistenti da essere manipolati e processati. Le microparticelle che costituiscono gli agglomerati sono denominate primarie. Gli agglomerati sono definiti “chimerici”, in quanto quando entrano a contatto con una minima quantità di acqua, disgregano ottenendo di nuovo le microparticelle primarie. Questa particolare caratteristica può essere sfruttata per formulare sistemi adatti alla somministrazione di farmaci a pazienti che presentano problemi di deglutizione. In questa tesi di dottorato sono presentate diverse applicazioni di questa tecnologia. In particolare, è stato studiato un sistema gastroresistente di mesalazina, in cui il farmaco è stato incapsulato in materiale lipidico, ottenendo delle microcapsule lipidiche. Per aumentarne la bagnabilità, le microcapsule sono state agglomerate con microparticelle di mannitolo e lecitina. Non si sono ottenute dei veri e propri agglomerati, ma microcapsule lipidiche rivestite da microparticelle di eccipienti. Inoltre è stato studiato un sistema estemporaneo di artemisinina e clindamicina per il trattamento della malaria. Inizialmente è stato prodotto il complesso di artemisinina con beta ciclodestrina attraverso la tecnica dello spray-drying. Successivamente sono stati prodotti degli agglomerati chimerici per vibrazione su setacci. Gli agglomerati di clindamicina e microparticelle di eccipienti sono stati formulati e caratterizzati. Infine , i due tipi di agglomerati saranno uniti per ottenere un’unica formulazione. Infine, è stata studiata una formulazione per la somministrazione buccale di levotiroxina per il trattamento dell’ipotiroidismo. Microparticelle di levotiroxina sodica ed eccipienti (mannitolo e lecitina) sono state prodotte con la tecnica dello spray drying. Le particelle primarie sono poi state trasformate in agglomerati chimerici. Questa agglomerati sono ideali per una somministrazione buccale in quanto si disgregano facilmente in presenza di una minima quantità di liquido come la saliva

From tablets to pharmaceutical nanotechnologies: Innovation in drug delivery strategies for the administration of antimalarial drugs

Malaria pharmacotherapy has slowly progressed from empirical concoctions to present-age multidrug treatments. Malaria therapy complexity is due to the necessity of using multiple drugs to counter the insurgence of parasite resistance, while preventing recrudescence. The recent inclusion in malaria pharmacotherapy guidelines of drugs with suboptimal physicochemical characteristics, primarily artemisinin and its derivatives, urgently calls for the application of technological innovations in drug delivery systems for malaria treatment. New formulation approaches for the combination of two or more drugs in a single medicinal dosage form, could provide innovative medicinal products, improve therapeutic outcomes and enhance patient compliance. The present review focuses on recent technological innovations applied to the co-formulation of antimalarial drugs in drug delivery systems. Solid dosage forms, such as tablets capable of delivering combination of drugs with individual release rates (Dome Matrix® technology) and multiparticulate forms, such as dispersible soft agglomerates are discussed. Furthermore, the application of pharmaceutical nanotechnology to malaria pharmacotherapy is evoked and outlined

Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery

Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0–66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine > stearyl alcohol > cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol > cetostearyl alcohol > stearylamine with LC50 of 24.7, 13.2 and 1.8 μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products

"Pierce and inhale" design in capsule based dry powder inhalers: Effect of capsule piercing and motion on aerodynamic performance of drugs

In this work three capsule-based dry powder inhalers, available for generics product development, were compared. Two technologically different dry powder formulations were used in order to relate the capsule piercing position and motion in the device to their aerodynamic performance. A "pierce and inhale" design, in which the capsules pierced with RS01, HandiHaler or Turbospin devices were aerosolized in the same device or transferred and aerosolized with another device, was constructed and carried out. The results obtained showed that the two dry powder formulations, i.e., a drug/lactose blend or a carrier-free powder, aerosolized using the capsule based inhalers, performed differently. The aerosolization of drug carrier mixture in terms of drug dispersion and emitted dose, was more sensible to the piercing and device combination than the carrier free powder. The motion of the capsule during the aerosolization boosted the powder emission, whereas the powder disaggregation was more influenced by the airflow pattern around the capsule and inside the inhaler turbulence chamber

Polymeric Films Loaded with Vitamin E and Aloe vera for Topical Application in the Treatment of Burn Wounds

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns