Poboljšana topljivost teško topljivog lijeka u čvrstim disperzijama s polimernim i nepolimernim hidrofilnim dodacima

Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small molecules (tartaric acid and mannitol) and polymeric additives (polyvinylpyrrolidone, PVP, and hydroxy propyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 g mL-1) was observed for tartaric acid (138 g mL-1) and PVP (103 g mL-1), respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy state in all cases, even with excipients having low glass transition temperature. Thermal methods (differential scanning calorimetry and hot stage microscopy) were used to evaluate the miscibility of the drug and additives. These techniques suggested that tartaric acid led to generation of ‘amorphous solutions’ in contrast to ‘amorphous suspensions’ in other three cases. The in vitro dissolution of IBS depended on the additive load and increased with increasing concentration in the case of tartaric acid, an acidifying excipient. The results indicate the suitability of even small molecules for providing solubility benefits, which can be attributed to the good glass forming ability and reasonable ability of IBS to remain in the glassy state.Irbesartan (IBS) je hidrofobni lijek teško topljiv u vodi koji se slabo oslobađa iz ljekovitih pripravaka. U radu je opisana priprava čvrstih disperzija (SDs) IBS-a pomoću aditiva male relativne molekulske mase (vinska kiselina i manitol) i polimera (polivinilpirolidona, PVP, i hidroksipropil metilceluloze, HPMC). Koristeći vinsku kiselinu i PVP topljivost je povećana 9,5 puta (138 g mL1), odnosno 7 puta (103 g mL1) u odnosu na kristaliničnu formu (14,6 g mL1). Difrakcijom X-zrakama praškastog uzorka potvrđeno je da je IBS uvijek u staklastom stanju, pa i s pomoćnim tvarima koje pri niskim temperaturama prelaze u staklasto stanje. Termičke metode (diferencijalna pretražna kalorimetrija i mikroskopija s vrućom pločom) korištene su za procjenu sposobnosti miješanja lijeka s aditivima. Rezultati ukazuju da vinska kiselina stvara amorfnu otopinu, a ostale tvari amorfne suspenzije. Oslobađanje IBS-a in vitro ovisi o količini aditiva i raste s povećanjem koncentracije vinske kiseline, (kisele pomoćne tvari). Poboljšanje topljivosti dodatkom malih molekula može se pripisati sposobnosti prelaska IBS-a u staklasto stanje i sposobnosti zadražavanja u tom stanju

Cutlines: UM Graduates

Background: Prenatal care/deliveries within our family medicine clinics have declined, perhaps because patients are unaware that our clinics provide these services. With lower volumes, clinicians may feel less comfortable with current skills/knowledge of obstetric (OB) care. Purpose: Increase family medicine clinic OB numbers, patient awareness, and clinician comfort/knowledge in OB. Methods: English-facile patients (18–50 years), residents and faculty at Aurora family medicine residency clinics were included. Patients were provided preintervention surveys upon check-in. Residents/faculty were surveyed via Survey Monkey. Changes made based on initial survey results were: 1) increasing systemwide awareness that our caregivers provide OB care, through fliers at emergency departments/urgent cares or posters in clinic waiting rooms; 2) keeping at least one same-day visit for OB patients; 3) distributing standard OB note templates to residents/faculty; and 4) placing patient educational handouts at each clinic. Patients, residents and faculty were reassessed at 9 months postintervention. Surveys were analyzed with Fisher’s exact tests. Results: Respondents to the preintervention survey included 83 patients, 26 residents and 19 faculty; 61 patients, 23 residents and 21 faculty responded to the postintervention survey. On both pre- and post-surveys, patients knew that their providers delivered babies (59% vs 57%, respectively; P = 0.86). However, only 22% and 33% of patients, respectively, had a doctor at our clinics deliver their baby or partner’s baby (P = 0.25). Even so, 95% and 100% of patients, respectively, would recommend their friends or family to our family practice clinics if they became pregnant (P = 0.14). On the pre-survey, 38% of residents felt clinic OB numbers were adequate versus 70% following intervention (P \u3c 0.05). On both pre- and post-surveys, residents planned on incorporating obstetric or prenatal care into their future practice (42% vs 52%, respectively; P = 0.57). On both pre- and post-surveys, faculty felt comfortable with OB skills and knowledge (53% vs 62%, respectively; P = 0.75). Lifestyle was the most common reason faculty gave for why they stopped doing deliveries (37% vs 33%, respectively). Conclusion: Implementation of changes to our OB workflow resulted in non-statistically significant improvements in viewpoints toward OB. Resident feelings of OB number adequacy significantly improved following intervention. Further study in multiple clinics could confirm the effectiveness and reasons for success of our interventions

Kvalitativna i kvantitativna analiza polimorfa klopidogrel bisulfata

This study deals with characterization and quantification of form I and form II of clopidogrel bisulphate (CLP), a selective and irreversible inhibitor of ADP-induced platelet aggregation. Thermal (DSC, TGA, HSM), crystallographic (XRD) and spectroscopic (FTIR) methods were used for characterization. After characterization of active pharmaceutical ingredient (API), these techniques were further used for identification of the polymorphic form present in three marketed formulations (tablets). FTIR method was successfully developed and validated for the quantification of form I in polymorph mixtures.U radu je opisana karakterizacija i kvantifikacija forme I i forme II klopidogrel bisulfata (CLP), selektivnog i ireverzibilnog inhibitora ADP-inducirane agregacije krvnih pločica. Za karakterizaciju su upotrebljene termičke (DSC, TGA, HSM), kristalografske (XRD) i spektroskopske (FTIR) metode. Nakon karakterizacije aktivne supstancije te metode su dalje upotrebljene za identifikaciju polimorfnih formi u ljekovitim oblicima (tri vrste registriranih tableta). Razvijena je i validirana FTIR metoda za određivanje forme I u smjesi polimorfa

Sexual dimorphism among medical students of north India assessed by interorbital circumference index

Background: The human body dimensions are affected by ecological, geographical, racial, gender, and age factors. Craniofacial anthropometry has become an important tool used in genetic counseling, reconstructive surgery, and forensic medicine. Orbital measurements are important in the evaluation of several systemic syndrome, craniofacial abnormalities, and also surgical treatment of post-traumatic telecanthus. Among these measurements, normal interpupillary distance, inner canthal distance (ICD), and outer intercanthal distance are the vital features to be known. Aims and Objectives: The aims and objectives of the present study were to assess the ICD, head circumference (HC), and circumference orbital index of male and female medical students of North India and find out gender differences in the respective parameters and thus to contribute the present finding to the available literature. Materials and Methods: This was an observational descriptive study conducted in the department of anatomy at a fixed time in 150 MBBS course students in the age group 18–22 years. The ICD and HC were measured using round end digital spreading Vernier caliper. Then, circumference interorbital index (CII) was calculated and analyzed. Results: The mean ICD in males was 3.44±0.33 mm and in females was 3.21±0.32 mm; mean HC in males was 56.03±1.55 mm and in females was 53.88±1.38 mm; and mean CII in males was 6.15±0.54 and in females was 5.95±0.51. Conclusion: The result of this study will help to establish the mean values for of craniofacial anthropometric parameters for medical students of North India, and the results are showing that craniofacial anthropometric parameters are sexually dimorphic

Calcific myofibrosis due to pentazocine abuse: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pentazocine, a synthetic narcotic analgesic, is commonly used for the relief of moderate to severe pain secondary to various conditions. It is usually well tolerated; however, adverse effects are not uncommon, especially when higher doses are used and when it is used in a dependent fashion. There have been reports of various complications associated with its use, including skin fibrosis, skin ulceration, abnormal skin pigmentation and symmetrical myopathy with fibrous myopathy. Fibrosis has usually been reported in the muscles at the site of injection of the drug. Being opioid in nature, it has a high abuse potential.</p> <p>Case presentation</p> <p>Here we report a case of pentazocine-induced calcific myofibrosis in a 42-year-old man involving muscles which were not injected with pentazocine.</p> <p>Conclusion</p> <p>This case highlights the care that needs to be taken when prescribing opioid analgesics, such as pentazocine, as routine painkillers. Patients who have history of substance abuse are more likely to abuse other agents, including prescription drugs. Rare consequences such as calcific myofibrosis are devastating and can cause significant lifelong disability.</p

Molecular Mobility and Physical Stability of Amorphous Irbesartan

Amorphous systems have attracted considerable attention due to their favorable properties; however, their stability issues still pose a major challenge. The purpose of the present work was to investigate the role of molecular mobility and moisture in the physical stability of a selected pharmaceutical amorphous system. Irbesartan (IBS), a relatively stable glass, was chosen as the model drug, as it exhibits a good physical stability (resistance to crystallization) at temperatures below the glass transition (Tg-50 K). The amorphous system was annealed at temperatures 298 K (25 °C) and 313 K (40 °C) at 0 and 75 % RH to study the effect of temperature and moisture on its relaxation behavior. Differential scanning calorimetry (DSC) was used to characterize both the crystalline and the freshly prepared glass, and to monitor the extent of relaxation at temperatures below glass transition (Tg) as well as heat capacity changes as a function of temperature. Molecular relaxation time constant (τ) decreased drastically from 302 years to 68 hours with the increase in annealing temperature as determined by Kohlrausch-William-Watts (KWW) equation. IBS was found to be ‘relatively’ stable in the amorphous state and presented a challenge for temporal measurements. Hence, at low annealing temperatures, (Tg-50 K or below) initial relaxation time (τ0) was estimated using the calorimetric based approach. Amorphous IBS was non-hygroscopic and retained its glassy nature under the accelerated stability conditions. The extent of relaxation in the amorphous drug in the presence of moisture was also estimated

Role of immunomarkers (P16 and Ki67) in identifying pre-malignant and malignant lesion of cervix: a comparative study

Background: Cancer of the cervix is the second most common cancer among women worldwide. Although pap test has successfully reduced the incidence of cervical cancer, it is associated with high false positive and high false negative test results. In order to improve the efficacy of screening program, United States cervical cancer screening guidelines recommend use of combined testing (cytology + HPV-DNA) in women above 30-65 years of age. However, due to application of current HPV vaccines, cervical screening will face challenges due to declining trends in the prevalence of HPV genotypes covered by vaccines. Aim: The study is aimed at finding out the role of immunomarkers (P16 and Ki67) in identifying pre-malignant and malignant lesion of carcinoma cervix and their comparison with the co-testing (cytology + HPV-DNA) method of screening. Methods: A cross-sectional observational study was conducted on 32 cases after consent. The tests done were cytology + HPV-DNA, cytology+p16, cytology+ Ki-67 and were compared in terms of their sensitivity, specificity, positive predictive value and negative predictive value against the gold standard, histopathology. Result: Majority of cases were in 30-40 years of age group. The sensitivity, specificity, positive predictive value and negative predictive value of cytology + HPV-DNA testing was 94.44%, 50%, 77.27%, 83.33% while that of cytology + P16 was 88.88%, 60%, 80%, 75% and cytology + Ki-67 was 88.88%, 100%, 100%, 91.66% respectively. Conclusion: Ki67 immunomarker is a better screening tool in terms of specificity, positive predictive value and negative predictive value when compared to cytology + HPV/p16. Ki-67 can be considered as a potential screening tool in future for both vaccinated and unvaccinated population