Reprint of "Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms".

Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300s(-1)) and injection moulding (approximately 900s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena.

Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms.

Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300 s(-1)) and injection moulding (approximately 900 s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena.

Synchronous intussusceptions following Roux-en-Y Gastric Bypass: case report and review of the literature.

Intussusception is an atypical cause of small bowel obstruction following Roux-en-Y gastric bypass and, as such, is not often considered in the differential diagnosis. In this setting, the pathophysiology appears to differ in that a pathologic lead point is rarely identified and the intussusceptum most often progresses retrograde into the proximal bowel. Involvement of the jejunojejunostomy is nearly universal in reported cases and, if untreated, can lead to devastating consequences. Despite this potential, the clinical presentation often lacks remarkable features yet timely surgical intervention is generally required. This phenomenon is being reported with greater frequency and altered motility in the Roux limb is the prevailing hypothesis regarding pathogenesis. Awareness of the potential for this process and prompt consultation with a bariatric surgeon are keys to optimal outcomes.

Chloroquine psychosis masquerading as PCP: a case report.

Chloroquine and its derivatives have been drugs of choice in the prophylaxis and treatment of malaria for over 50 years. These drugs are also frequently used in the treatment of various rheumatologic disorders. Because many Americans now travel abroad and may require chloroquine prophylaxis, as well as the fact that such medications are readily available through Internet-based supply houses, clinicians should be aware of the potential toxicity associated with the use of these agents. We present the case of an adolescent female who presented with acute, chloroquine-induced toxic psychosis resembling that induced by phencyclidine (PCP) in clinical presentation and laboratory findings. In the acute setting, the differentiation between chloroquine toxic psychosis and PCP psychosis may be difficult. Therefore, the syndrome of chloroquine-induced psychosis is reviewed and its differentiation from PCP psychosis highlighted as it relates to important aspects of this case.

Buprenorphine maintenance: a new treatment for opioid dependence.

Buprenorphine (Subutex) is a safe and effective treatment for opioid dependence, and has very low potential for abuse, especially when it is combined with naloxone (Narcan) in a single sublingual tablet (Suboxone). New regulations allow physicians who are certified in buprenorphine therapy to offer it in their offices, a development that can substantially increase patient access to treatment.

Patient-provider e-mail communication as an adjunctive tool in addiction medicine.

Frequent electronic mail communication between patients and their addiction specialist can be utilized as an adjunct in the treatment of alcohol or substance dependency. Selected patients benefit from mandatory daily electronic mail communications with their provider through enhanced accountability, frequent self-assessment, deterrents to isolation, and a sense of continuous access to care. Participants have found the experience easy and enjoyable and all have maintained continuous sobriety. We present our experience using this modality as a series of illustrative case reports and a discussion of the implications of using electronic mail with patients in addiction medicine.

Anabolic-androgenic steroid abuse by physicians.

Physicians are not immune to the rising popularity of anabolic-androgenic steroid (AAS) abuse. We present three cases of physician-patients who recently required inpatient substance abuse treatment stemming from the abuse of AAS or related compounds. These individuals shared a number of clinical and psychological features that led to or resulted from their abuse of ergogenic substances. Each incurred severe professional, legal, domestic and/or health consequences as a result of their abuse. The common features identified in these patients suggest the presence of an overriding "risk behavior syndrome" that may predispose susceptible individuals to AAS abuse. The reinforcing properties of AAS and the potential for dependence remains an active area of research. Effective treatment of these individuals requires recognition of the causative factors as well as the high likelihood of other substance abuse that must also be addressed. With proper support and monitoring, these individuals can resume productive professional careers.

Drug adjuncts for treating alcohol dependence.

Three drugs are approved by the US Food and Drug Administration for treating alcoholism: disulfiram, naltrexone, and acamprosate. Drugs approved for other indications that are being used experimentally or "off-label" include nalmafene, topiramate, and ondansetron. As we learn more about the pathophysiologic basis of alcoholism, it is hoped that novel drugs can be developed to help people with alcohol dependence achieve abstinence, and as a result, curb alcohol-related morbidity.

Chemical dependency treatment outcomes of residents in anesthesiology: results of a survey.

Substance abuse is a potentially lethal occupational hazard confronting anesthesiology residents. We present the results of a survey sent to all United States anesthesiology training programs regarding experience with and outcomes of chemically dependent residents from 1991 to 2001. The response rate was 66%. Eighty percent reported experience with impaired residents and 19% reported at least one pretreatment fatality. Despite this familiarity, few programs required pre-employment drug testing or used substance abuse screening tools during interviews. The majority of impaired residents attempted reentry into anesthesiology after treatment. Only 46% of these were successful in completion of anesthesiology residency. Eventually, 40% of residents who underwent treatment and returned to medical training entered another specialty. The mortality rate for the remaining anesthesiology residents was 9%. Long-term outcome was reported for 93% of all treated residents. Of these, 56% were successful in some specialty of medicine at the end of the survey period. We hypothesize that specialty change afforded substantial improvement in the overall success rate and avoided significant mortality. Redirection of rehabilitated residents into lower-risk specialties may allow a larger number to achieve successful medical careers.

A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier.

Blood-brain barrier endothelial cells are characterized by the presence of tight intercellular junctions, the absence of fenestrations, and a paucity of pinocytotic vesicles. The in vitro study of the BBB has progressed rapidly over the past several years as new cell culture techniques and improved technologies to monitor BBB function became available. Studies carried out on viable in vitro models are set to accelerate the design of drugs that selectively and aggressively can target the CNS. Several systems in vitro attempt to reproduce the physical and biochemical behavior of intact BBB, but most fail to reproduce the three-dimensional nature of the in vivo barrier and do not allow concomitant exposure of endothelial cells to abluminal (glia) and lumenal (flow) influences. For this purpose, we have developed a new dynamic in vitro BBB model (NDIV-BBB) designed to allow for extensive pharmacological, morphological and physiological studies. Bovine aortic endothelial cells (BAEC) developed robust growth and differentiation when co-cultured alone. In the presence of glial cells, BAEC developed elevated Trans-Endothelial Electrical Resistance (TEER). Excision of individual capillaries proportionally decreased TEER; the remaining bundles were populated with healthy cells. Flow played an essential role in EC differentiation by decreasing cell division. In conclusion, this new dynamic model of the BBB allows for longitudinal studies of the effects of flow and co-culture in a controlled and fully recyclable environment that also permits visual inspection of the abluminal compartment and manipulation of individual capillaries.