Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Recognizing the Value of Teaching Proverbs: Multicultural Origins of Oral and Written Literacy

The purpose of this paper is to explore the use of multicultural proverbs in interdisciplinary and cross-cultural instruction through the language arts, history and social sciences. Educators can use proverbs to engage students in learning, enhance their understanding of other cultures and languages, and promote a globally-sensitive community.

Prevention of oral lesions in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children and is responsible for severe stomatologic complications. Treatment consists of four phases of chemotherapy, the main side effect of methotrexate, the drug most used during the intensification phase, is oral mucositis. OBJECTIVE: To evaluate the clinical aspects of the oral mucosa of children with ALL and to determine the effect of 0.12% chlorhexidine gluconate on the prevention of stomatologic complications in these patients. PATIENTS AND METHODS: Thirty-three children treated for ALL ranging in age from 2 to 15 years, without distinction of gender or race, were submitted to visual examination, digital palpation of the oral mucosa and cytologic examination of the buccal mucosa, and divided into two groups: group I consisted of 23 children using an oral solution of 0.12% chlorhexidine gluconate twice a day, and group II consisted of 10 children who did not receive this solution. All children received daily oral hygiene care guided by the dentist throughout treatment. RESULTS: Mucositis was observed in six children of group I and eight of group II, and was characterized by erythema, edema and ulcers. Uniform cytologic findings were obtained for the two groups, with a clear predominance of cells of the intermediate layer in all smears, in addition to a perinuclear halo in 18% of the smears. CONCLUSION: The present results suggest that systematic preventive treatment with 0.12% chlorhexidine gluconate and oral hygiene care reduce the occurrence of oral complications in children with ALL undergoing antineoplastic chemotherapy.

Prevention of oral lesions in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children and is responsible for severe stomatologic complications. Treatment consists of four phases of chemotherapy, the main side effect of methotrexate, the drug most used during the intensification phase, is oral mucositis. OBJECTIVE: To evaluate the clinical aspects of the oral mucosa of children with ALL and to determine the effect of 0.12% chlorhexidine gluconate on the prevention of stomatologic complications in these patients. PATIENTS AND METHODS: Thirty-three children treated for ALL ranging in age from 2 to 15 years, without distinction of gender or race, were submitted to visual examination, digital palpation of the oral mucosa and cytologic examination of the buccal mucosa, and divided into two groups: group I consisted of 23 children using an oral solution of 0.12% chlorhexidine gluconate twice a day, and group II consisted of 10 children who did not receive this solution. All children received daily oral hygiene care guided by the dentist throughout treatment. RESULTS: Mucositis was observed in six children of group I and eight of group II, and was characterized by erythema, edema and ulcers. Uniform cytologic findings were obtained for the two groups, with a clear predominance of cells of the intermediate layer in all smears, in addition to a perinuclear halo in 18% of the smears. CONCLUSION: The present results suggest that systematic preventive treatment with 0.12% chlorhexidine gluconate and oral hygiene care reduce the occurrence of oral complications in children with ALL undergoing antineoplastic chemotherapy.

Genome-wide Study of Oral Cavity and Pharyngeal Cancer

Peer reviewed

Safety and Efficacy of Oral Fexofenadine in Children with Seasonal Allergic Rhinitis - a Pooled Analysis of Three Studies

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

Impact of oral diseases and disorders on oral health-related quality of life of preschool children

BACKGROUND The presence of oral diseases and disorders can produce an impact on the quality of life of preschool children and their parents, affecting their oral health and well-being. However, socioeconomic factors could confound this association, but it has not been yet tested at this age. OBJECTIVE To assess the impact of early childhood caries (ECC), traumatic dental injuries (TDI) and malocclusions on the oral health-related quality of life (OHRQoL) of children between 2 and 5 years of age adjusted by socioeconomic factors. METHODS Parents of 260 children answered the Early Childhood Oral Health Impact Scale (ECOHIS) (six domains) on their perception of the children's OHRQoL and socioeconomic conditions. Two calibrated dentists (κ>0.8) examined the severity of ECC according to dmft index, and children were categorized into: 0=caries free; 1-5=low severity; ≥6=high severity. TDI and malocclusions were examined according to Andreasen & Andreasen (1994) classification and for the presence or absence of three anterior malocclusion traits (AMT), respectively. OHRQoL was measured through ECOHIS domain and total scores, and poisson regression was used to associate the different factors with the outcome. RESULTS In each domain and overall ECOHIS scores, the severity of ECC showed a negative impact on OHRQoL (P<0.001). TDI and AMT did not show a negative impact on OHRQoL nor in each domain (P>0.05). The increase in the child's age, higher household crowding, lower family income and mother working out of home were significantly associated with OHRQoL (P<0.05). The multivariate adjusted model showed that the high severity of ECC (RR=3.81; 95% CI=2.66, 5.46; P<0.001) was associated with greater negative impact on OHRQoL, while high family income was a protective factor for OHRQoL (RR=0.93; 95% CI=0.87, 0.99; P<0.001). CONCLUSIONS The severity of ECC and a lower family income had a negative impact on the OHRQoL of preschool children and their parents.

The role of games in the development of oral skills in Teaching english as a foreign language to adult learners from An extension course at Universidad del Valle [recurso electr?nico]

This research arose from the notorious need to promote oral production in the adult learners of the English Extension courses at Universidad del Valle in 2014. This qualitative research was carried out in a 60 hour course divided along 15 sessions on Saturdays, and with an adult population between the ages of 22 and 65 years old. Its main objective was to describe the impact of games aimed at promoting oral production in English with a group of adult learners. Data were collected from one demographic survey, video-recordings of classroom events during the implementation of games, students? surveys after each game and a teacher?s journal. The analysis of data showed that games did have an impact in students? performance which was related to a positive atmosphere in the classroom. Students showed progress in terms of fluency, interaction and even pronunciation; however they still showed difficulties with accuracy in their spontaneous utterances. These learners? achievements seemed to have a relation with the class atmosphere during games where students showed high level of involvement, confidence, mutual support and enjoyment.

Ventricular Fibrillation in Patient with Multi-vessel Coronary Spasm Four Days after the Initiation of Oral Beta-blocker

We describe a case of ventricular fibrillation occurring in a patient with multi-vessel coronary spasm after the initiation of an oral beta-blocker. A 56-year-old man began to experience chest discomfort and his computed tomography revealed intermediate coronary stenoses. He was administered medications including an oral beta-blocker but suddenly collapsed while walking 4 days later. An automated external defibrillator detected ventricular fibrillation and delivered successful electrical cardioversion. An acetylcholine provocation test after stabilization of the status revealed triple-vessel coronary spasm. Beta-blockers may provoke exacerbation of coronary spasm and result in lethal arrhythmia.

The treatment of oral lesions in Behçet's Syndrome: case report

Behçet's disease (BD) is a multi-systemic vascular disorder characterized by oral and genital ulcers, cutaneous, ocular, arthritic, vascular, central nervous system and gastrointestinal involvement. It usually affects young adults and the etiopathogenesis is unknown. A 21-year-old girl, Caucasian, with diagnostic BD, presented with rheumatoid arthritis, genital lesions and multiple recurrent ulcers inside the mouth, with an erythematous halo, covered by yellowish exudates exacerbated during menstrual periods, and in situations of stress and anxiety. The application of low power laser in ulcers was considered in order to decrease the inflammatory symptoms and pain, beyond getting the healing process accelerated. The proposed therapy was able to promote pain relief, increase local microcirculation and repair ulcerated lesions, eliminating the need for administration of systemic or topical medications, leading to improved quality of life.

Use of oral rehydration therapy in the treatment of childhood diarrhoea in Douala, Cameroon

Introduction The use of oral rehydration solutions in our context remains limited. This study was conducted to analyze the rate of this use in Douala, Cameroon and thereby determine the factors associated with it. Method A cross-sectional survey was administered to parents of children aged five years and younger during a six-month study period. The studied variables focused on the socio-demographic data of the population, data on diarrhoea and its severity, data on oral rehydration salts (ORS), and data related to other interventions for diarrhoea. The chi-square test was used to qualify associations between variables, with the significance level being set at 5%. Results Overall, 672 people agreed to participate in the study. Among them, 418 (62.2%) correctly defined diarrhoea. When their children develop diarrhoea, the majority of the parents (348, 51.8%) reported seeking hospital assistance before any intervention, while 225 parents (33.5%) preferred the use of ORS first. Four hundred seventy-five parents (70.7%) had heard of ORS and among them 313 (65.9%) had actually given ORS to their children as treatment during these children’s most recent episodes of diarrhoea. Of the parents who had given their children ORS, 217 (69.3%) knew how to prepare it, and 122 (39.0%) knew how to administer it. One hundred thirty-five parents (20.1%) had administered metronidazole to treat their children’s diarrhoea. The age of the children, the parents’ level of education, and the number of children in the household significantly influenced the use or non-use of ORS (respectively, p < 0.001, p = 0.003 and p < 0.0001). Rehydration was correctly identified by 234 parents (34.8%) as the purpose of administering ORS. Conclusion The knowledge and the use of ORS in diarrhoea by the study sample was insufficient. The role of ORS was poorly known. Awareness campaigns can be carried out in order to improve the use of this effective intervention for diarrhoea.

Integration of oral health into primary care : a scoping review protocol

Integrated care has been introduced as a means of improving health outcomes and access to care, and reducing the cost of healthcare. Despite its importance, the integration of oral health into primary care is still an emerging healthcare pathway. This scoping review protocol has been developed and funded by the Canadian Institutes of Health Research to provide an evidence-based synthesis on a primary oral healthcare approach and its effectiveness in improving oral health outcomes.

Integration of oral health into primary care : a scoping review protocol

Integrated care has been introduced as a means of improving health outcomes and access to care, and reducing the cost of healthcare. Despite its importance, the integration of oral health into primary care is still an emerging healthcare pathway. This scoping review protocol has been developed and funded by the Canadian Institutes of Health Research to provide an evidence-based synthesis on a primary oral healthcare approach and its effectiveness in improving oral health outcomes.

Suullisen perinteen tekstualisaatio ja moderni kontekstualisaatio Suomessa : projektikuvaus

Ajankohtaista