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This work describes the first development of high-concentration suspension formulations of human immune globulin. Colloidal-level dispersions of immune globulin were achieved by suspending a spray dried solid powder of protein in a protein solution made saturated by the addition of pharmaceutical excipients. The spray drying process was used to generate ∼90 % of particles below 20μ. The monomer and aggregates content of immunoglobulin were found to be 93 % and 0.3 %, respectively. The injection forces for the colloidal suspensions were characterized using a dynamic compression test. The concentrations of 300, 380, and 400 mg/mL formulations were injected at 3.8 N, 10 N, and 16.5 N of maximum injection forces, respectively, when a 24-gauge needle was used. The viscosity of a 300 mg/mL suspension was 128 cP. The viscosity of a 380 mg/mL suspension was 284 cP, and the viscosity was higher for the 400 mg/mL formulation; however, injectability was not an issue, which remains rare for non-Newtonian, shear-thickening systems. It is acknowledged that the 400 mg/mL suspension formulation remained relatively challenging as compared to other suspensions for injection because of its very high viscosity, and significant force was required to inject it. We show that where ultra-high-concentration immune globulin is being developed within reasonable constraints of pharmaceutical regulation, with an injectability parameter, formulations might make their way to the clinic when viscosity could say otherwise. However, further work should be conducted to assess chemical stability (using methods such as mass spectrometry) along with forced degradation studies prior any clinical use., Competing Interests: Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Needle crystals can cause filtering and handling problems in industrial settings, and the factors leading to a needle crystal morphology have been investigated. The crystal growth of the amide and methyl, ethyl, isopropyl, and t-butyl esters of diflunisal have been examined, and needle growth has been observed for all except the t-butyl ester. Their crystal structures show that the t-butyl ester is the only structure that does not contain molecular stacking. A second polymorph of a persistent needle forming phenylsulfonamide with a block like habit has been isolated. The structure analysis has been extended to known needle forming systems from the literature. The intermolecular interactions in needle forming structures have been analyzed using the PIXEL program, and the properties driving needle crystal growth were found to include a 1D motif with interaction energy greater than -30 kJ/mol, at least 50% vdW contact between the motif neighbors, and a filled unit cell which is a monolayer. Crystal structures are classified into persistent and controllable needle formers. Needle growth in the latter class can be controlled by choice of solvent. The factors shown here to be drivers of needle growth will help in the design of processes for the production of less problematic crystal products., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Living with a progressive disease as muscular dystrophy (MD) can be challenging for the patient and the entire family from both emotional and practical point of view. We aimed to extend our previously published data about mental health in patients with MDs, also investigating coping profiles of both themselves and their parents. Furthermore, we wanted to verify whether psychological adaptation of patients can be predicted by coping strategies, taking also into account physical impairment, cognitive level and socioeconomic status., Methods: 112 patients with MDs, aged 2-32 were included. Their emotional and behavioural features were assessed through parent- and self-report Achenbach System for Empirically Based Assessment questionnaires and Strength and Difficulties Questionnaires. Development and Well-Being Assessment or Autism Diagnostic Observation Schedule were administered to confirm suspected diagnoses. Coping profile of both parents and patients was assessed through the self-administered New Italian Version of the Coping Orientation to the Problems Experienced questionnaire and its relationship with emotional/behavioural outcome was examined in linear regression analyses., Results: High prevalence of intellectual disability and autism spectrum disorders was confirmed in Duchenne MD. Despite the high rate of internalizing symptomatology, we did not report higher rate of psychopathological disorders compared to general population. Parents tend to rely more on positive reinterpretation and less on disengagement coping. Avoidance coping, whether used by parents or patients, and ID, predicted increased emotional/behavioural problems., Conclusions: Psychosocial interventions should address problems of anxiety and depression that people with MDs frequently experience, even through fostering parents' and childrens' engagement coping over disengagement coping.

Understanding phase transitions in pharmaceutical materials is of vital importance for drug manufacturing, processing and storage. In this paper we have carried out comprehensive high-resolution spectroscopic studies on the polymorphs of the non-steroidal anti-inflammatory drug diflunisal that has four known polymorphs, forms I-IV (FI-FIV), three of which have known crystal structures. Phase transformations during milling, heating, melt-quenching and exposure to high relative humidity were investigated using Raman and terahertz spectroscopy in combination with differential scanning calorimetry and X-ray powder diffraction. The observed phase transformations indicate the stability order FIII>FI>FII, FIV. Furthermore, crystallization experiments from the gas phase and from solution by fast evaporation of different solvents were carried out. Fast evaporation of an ethanolic solution below 70°C was identified as a reliable and convenient method to obtain the somewhat elusive FII in bulk quantities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To evaluate through a comprehensive protocol, the psychopathological profile of DMD boys. The primary aim of this observational study was to describe the emotional and behavioural profile and the neurodevelopmental problems of Italian boys with Duchenne Muscular Dystrophy (DMD); the secondary aim was to explore the relation between psychopathological profile and DMD genotype., Method: 47 DMD boys, aged 2-18, were included in the study and assessed through structured and validated tools including Wechsler scales or Griffiths for cognitive ability, Child Behavior Check List (CBCL), Youth Self Report (YSR) and Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural features. Patients "at risk" based on questionnaires scores were evaluated by a clinical structured interview using Development and Well Being Assessment (DAWBA) or Autism Diagnostic Observation Schedule (ADOS), as required., Results: The 47 enrolled patients, defined with a Full Scale Intelligence Quotient (FSIQ) of 80.38 (one SD below average), and presenting a large and significant difference in FSIQ in relation to the site of mutation along the dystrophin gene (distal mutations associated with a more severe cognitive deficit), were showing Internalizing Problems (23.4%) and Autism Spectrum Disorders (14.8%). Interestingly, an association of internalizing problems with distal deletion of the DMD gene is documented., Conclusion: Even though preliminary, these data show that the use of validated clinical instruments, that focus on the impact of emotional/behaviour problems on everyday life, allows to carefully identify clinically significant psychopathology., (Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

This paper describes the psycho-social treatments received by 502 patients with MDs and their relatives, and the costs for care sustained by the families in the previous six month period. Data were collected by the MD-Care Schedule (MD-CS) and the Family Problems Questionnaire (FPQ). Psycho-educational interventions were provided to 72 patients (14.3%), and social/welfare support to 331 patients (65.9%). Social/welfare support was higher in patients with DMD or LGMD, in those showing more severe disability, and in patients who were in contact with centres located in Northern Italy. Psycho-educational interventions were received by 156 (31%) relatives, and social/welfare support by 55 (10.9%) and mainly provided by Family/Patients Associations (83.6%). Relatives with higher educational levels, who spent more daily hours in the assistance of patients with DMD, and in contact with centres in Central Italy more frequently benefited from psycho-educational interventions. In the previous year, costs for care were sustained by 314 (63.9%) relatives. Financial difficulties related to patient's condition, were higher in families of patients who needed more intensive rehabilitation and daily hours of caregiving, and in families who lived further away from the reference's centre. These results showed that psycho-social aspects of MDs care are only partially met in Italy, and that ad hoc supportive interventions for these patients and their families should be potentiated.

This paper describes the pharmacological therapies and rehabilitative interventions received by 502 patients with Muscular Dystrophies, evaluated in relation to patient's socio-demographic and clinical variables, and geographical areas. Data were collected by the MD-Socio-Demographic and Clinical Schedule (MD-SC-CS) and by the Family Problems Questionnaire (FPQ). The most part of the enrolled patients were in drug treatment. The number of the medications increased in relation to patient's age, disability degree and duration of illness and was higher among patients with Duchenne Muscular Dystrophy (DMD) compared with Becker (BMD) or Limb-Girdle Muscular Dystrophies (LGMD). Steroids (deflazacort or prednisone) were the drug most frequently used, followed by cardiologic and bone metabolism drugs. In general, patients using steroids were younger and had a shorter duration of illness; patients using cardiac drugs and dietary supplements were older and had a longer duration of illness. Rehabilitative interventions were provided to about 70% (351/502) of patients, mainly DMD. Of these, physiotherapy was the more frequent treatment (96.6%) and was prevalently performed in rehabilitative centres (about 70% of patients) and at home in only 30%. Hydrokinetic-therapy was practiced by 6.8% of patients. Respiratory rehabilitation was provided to 47.0% of patients (165/351) and assisted mechanical ventilaventilation to 13.1% (46). The amount of rehabilitative interventions increased in relation to the patient's age, level of disability and duration of illness. Compared to Central and Northern Italy, in Southern Italy there was a higher attention to cardiological impairment as shown by a higher number of patients receiving heart drugs. No statistically significant differences concerning the possibility to have access to rehabilitative interventions were noted among the three geographical areas. However, patient living in Southern Italy tend to receive rehabilitation more often at home.

Introduction: This study explores burden and social and professional support in families of young patients with muscular dystrophies (MDs) in Italy., Methods: The study was carried out on 502 key relatives of 4- to 25-year-old patients suffering from Duchenne, Becker, or Limb-Girdle MD who were living with at least 1 adult relative., Results: A total of 77.1% of relatives reported feelings of loss, 74.0% had feelings of sadness, and 59.1% had constraints in leisure activities. Burden was higher among relatives of patients with higher disability and who spent more daily hours in caregiving. Practical difficulties were higher among relatives who perceived lower help in patient emergencies and less practical support by their social network. Psychological burden was higher in those relatives who were unemployed, those with poorer support in emergencies, and those with lower social contacts., Conclusions: Caring for patients with MDs may be demanding for relatives even in the early stages of these disorders, especially when social support is poor and the patient's disability increases., (© 2014 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.)

This study explored the burden in parents and healthy siblings of 4-17 year-old patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, and whether the burden varied according to clinical aspects and social resources. Data on socio-demographic characteristics, patient's clinical history, parent and healthy children burden, and on parent's social resources were collected using self-reported questionnaires administered to 336 parents of patients with DMD (246) and BMD (90). Parents of patients with DMD reported higher burden than those of patients with BMD, especially concerning feeling of loss (84.3% DMD vs. 57.4% BMD), stigma (44.2% DMD vs. 5.5% BMD) and neglect of hobbies (69.0% DMD vs. 32.5% BMD). Despite the burden, 66% DMD and 62.4% BMD parents stated the caregiving experience had a positive impact on their lives. A minority of parents believed MD has a negative influence on the psychological well-being (31.0% DMD vs. 12.8% BMD), and social life of unaffected children (25.7% vs. 18.4%). In the DMD group, burden correlated with duration of illness and parent age, and burden was higher among parents with lower social contacts and support in emergencies. In DMD, difficulties among healthy children were reported as higher by parents who were older, had higher burden and lower social contacts. In both groups, burden increased in relation to patient disability. These findings underline that the psychological support to be provided to parents of patients with MD, should take into account clinical features of the disease.

A group of 42 Italian boys with Duchenne Muscular Dystrophy was compared with a control group of 10 boys with Spinal Muscular Atrophy and Osteogenesis Imperfecta on tests assessing general intellectual ability, language, neuropsychological functions, and reading skills with the aim of describing a comprehensive profile of the various functions and investigating their interrelationships. The influence of general intellectual level on performance was analyzed. Further, correlations between various neuropsychological measures and language performances were computed for the group with Duchenne Muscular Dystrophy, as well as the correlations between reading scores and other cognitive and linguistic measures. A general lowering in VIQ, PIQ, and FSIQ scores was found to characterize the group with Duchenne Muscular Dystrophy. Expressive language skills were within the normal range, while syntactic and grammatical comprehension were significantly impaired. The presence of below-average reading performances was further confirmed. However, unlike previous studies on irregular orthographies, the present results show that (a) the mild reading difficulties found in the sample essentially concern speed rather than accuracy; (b) they concern word rather than nonword reading; (c) lower reading performances are related to lower scores in general IQ; (d) no correlations emerge with phonological abilities, verbal short-term memory, or working memory, but rather with long-term memory and lexical skills. This may suggest that language-specific effects modulate the cognitive expressions of Duchenne Muscular Dystrophy and raises the possibility that the dysfunctions underlying the reading difficulties observed in affected readers of regular orthographies involve different neurocognitive systems than the cortico-cerebellar circuits usually invoked.

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing., (Copyright © 2011 Elsevier Inc. All rights reserved.)