Roller compaction process development and scale up using Johanson model calibrated with instrumented roll data

Roller compaction is a dry granulation process used to convert powder blends into free flowing agglomerates. During scale up or transfer of roller compaction process, it is critical to maintain comparable ribbon densities at each scale in order to achieve similar tensile strengths and subsequently similar particle size distribution of milled material. Similar ribbon densities can be reached by maintaining analogous normal stress applied by the rolls on ribbon for a given gap between rolls. Johanson (1965) developed a model to predict normal stress based on material properties and roll diameter. However, the practical application of Johanson model to estimate normal stress on the ribbon is limited due to its requirement of accurate estimate of nip pressure i.e. pressure at the nip angle. Another weakness of Johanson model is the assumption of a fixed angle of wall friction that leads to use of a fixed nip angle in the model. To overcome the above mentioned limitations, we developed a novel approach using roll force equations based on a modified Johanson model in which the requirement of pressure value at nip angle was eliminated. An instrumented roll on WP120 roller compactor was used to collect normal stress data measured at three locations across the width of a roll (P1, P2, P3), as well as gap and nip angle data on ribbon for placebo and various active blends along with corresponding process parameters. The nip angles were estimated directly using experimental pressure profile data of each run. The roll force equation of Johanson model was validated using normal stress, gap, and nip angle data of the placebo runs. The calculated roll force values compared well with those determined from the roll force equation provided for the Alexanderwerk(?) WP120 roller compactor. Subsequently, the calculation was reversed to estimate normal stress and corresponding ribbon densities as a function of gap and RFU (roll force per unit roll width). A placebo model was developed and calibrated using a subset of placebo run data obtained on WP120. The roll force values were calculated using vendor supplied equation. The nip angle was expressed as a function of gap and RFU. The nip angle, gap and RFU were used in a new roll force equation to estimate normal stress P2 at the center of the ribbon. Using ratios P1/P2 and P3/P2 from the calibration data set, P1 and P2 were estimated. The ribbon width over which P1, P2, and P3 are effective was determined by minimizing sum square error between the model predicted vs. experimental ribbon densities of the calibration set. The model predicted ribbon densities of the placebo runs compared well with the experimental data. The placebo model also predicted with reasonable accuracy the ribbon densities of active A, B, and C blends prepared at various combinations of process parameters. The placebo model was then used to calculate scale up parameters from WP120 to WP200 roller compactor. While WP120 has a single screw speed, WP200 is equipped with a twin feed screw system. A limited number of roller compaction runs on WP200 was used as a calibration set to determine normal stress profile across ribbon width. The nip angle equation derived from instrumented roll data collected on WP120 was applied to estimate nip angles on WP200 at various processing conditions. The roll force values calculated from vendor supplied equation and the nip angle values were used in roll force equation to estimate normal stress P2 at the tip of the feed screws. Based on feed screw design, it was assumed that the normal stress at the center of the ribbon was equal to those calculated at the tip of the feed screws. The ratio of normal stress at the edge of the ribbon Pe to the normal stress P2 at the feed screw tip was optimized to minimize sum square error between model predicted vs. experimental ribbon densities of the calibration set. The model predicted ribbon densities of the batches prepared on WP200 compared well with the experimental data thus indicating success of the scale up procedure. For the demonstration purpose, the model was also calibrated using instrumented roll data of active C batches. This would be applicable when sufficient amount of API is available or placebo model cannot predict ribbon density of active batches.     

Pharyngocutaneous fistula after anterior cervical spine surgery

Pharyngocutaneous fistulae are rare complications of anterior spine surgery occurring in less than 0.1% of all anterior surgery cases. We report a case of a 19 year old female who sustained a C6 burst fracture with complete quadriplegia. She was treated urgently with a C6 corpectomy with anterior cage and plating followed by posterior cervical stabilization at another institution. Post operatively she developed a pharyngocutaneous fistula that failed to heal despite several attempts of closure and esophageal exclusion with a Jpeg tube. The patient was eventually successfully treated with a three-stage procedure consisting of firstly a posterior approach to reinforce the posterior stabilization of the cervical spine that was felt to be inadequate, secondly an anterior approach with removal of all the anterior instrumentation followed by iliac crest bone graft and thirdly a superior based sternocleidomastoid flap that was interposed between the esophagus and the anterior cervical spine. The patient's fistula healed successfully. However, yet asymptomatic, the anterior iliac crest bone graft resorbed almost completely at 16 months follow up. In light of this complication, we discuss the surgical options for the treatment of pharyngocutaneous fistulae and the closure of this fistula using a superiorly based sternocleidomastoid muscle flap.     

Impact of Body Mass Index on Left Ventricular Function

Background

Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function.

Methods

Fifty one obese and 25 normal weight, serving personnel without any other pathological condition were studied. Group I (n=25) consisted of subjects with normal weight and body mass index (BMI <25kg/m²), Group II (n=34) of overweight subjects (BMI 25-29.9 kg/m²) and Group III (n=17) of obese subjects (BMI >30 kg/m²). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by ≥ 2 SD from the normal weight group.

Result

Ejection fraction, fractional shortening were increased (p<0.05) in Group II and III. Left ventricular dimensions were increased (p< 0.001) but relative wall thickness was unchanged. Systolic dysfunction was not observed in any of the obese patients. The mitral valve pressure half time (p< 0.01), left atrial diameter (p < 0.01) and the deceleration time were increased (p< 0.01) in obese subjects, while other diastolic variables were unchanged. No difference were found between obesity subgroups. Subclinical diastolic dysfunction was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function.

Conclusion

Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.Key Words: Obesity, Systolic function, Diastolic function, Echocardiography     

Preclinical dementia: an Italian multicentre study on amnestic mild cognitive impairment

BACKGROUND: Different rates and cognitive predictors of conversion to dementia have been reported in subjects with different kinds of mild cognitive impairment (MCI). METHODS: A prospective, 24-month follow-up study, involving 269 subjects who strictly fulfilled criteria for the amnestic MCI. RESULTS: Conversion rate to dementia was 21.4% per year. Seventy-nine out of the 83 individuals who developed dementia were affected by probable Alzheimer's disease (AD). Among others, at the 24-month follow-up 24.1% were still affected by amnestic MCI, 13.3% had changed their neuropsychological profile of impairment and 17.2% were cognitively normalised. Compared to subjects who did not convert to AD, those who did convert showed poorer immediate and delayed recall and recognition of verbal and visual material at baseline as well as reduced executive abilities. A combination of age, Clinical Dementia Rating boxes and scores on delayed recall and recognition of verbal and visual material accurately identified 86% of the subjects who developed AD. CONCLUSIONS: Elderly subjects affected by an isolated memory disorder have a high probability of developing AD. The ability of verbal and visual measures to predict incipient dementia of memory impairment may be increased by the simultaneous assessment of individual features, such as age or rate of functional impairment.