Studies in child psychiatric epidemiology have begun to focus far

Studies in child selleck kinase inhibitor psychiatric epidemiology have begun to focus far more on identifying explanations for specific patterns of comorbidity than simply documenting that, comorbidity is pervasive.63 Substance use disorders Trends of drug and alcohol use in high-school youth in the US arc carefully monitored by studies such as Monitoring the Future (MTF).65 The 2007 MTF survey that, encompassed nearly 50 000 8th-, 10th-, and 12th-gra.de students in over 400 secondary schools nationwide continues to show a decline in illicit drug use across the US. However, this survey Inhibitors,research,lifescience,medical does not collect information on substance use disorders. The median estimate of alcohol or drug

abuse or dependence in community surveys of adolescents is 5% with a range from 1% to 24%. 8 The results of the recent studies described in Table I yield similar estimates: 4.7%,13 5.3%, 14 2.4%, 12 and 1.7%.15 The lower Inhibitors,research,lifescience,medical rates in the latter two studies are likely to be attributed to the lower age range of these samples. For example, in the Great Smoky Mountains Survey, there was a dramatic increase in the rates of substance use disorders with age, with a 3-month prevalence rate of 0.3% at age 13,1.4% at age 14,5.3% at age 15, and 7.6% at age 16. Gender differences in prevalence rates of substance use disorders are inconsistent. Whereas several studies show Inhibitors,research,lifescience,medical equal prevalence rates in males and females,13 others show that males have greater rates than

females.14 Substance use disorders have been generally Inhibitors,research,lifescience,medical shown to be more common in white youths, and equally distributed by parental social class.66

Risk factors for mental disorders in youth Aside from providing extensive information on regional differences in mental disorders in the US, the majority of prior population studies of mental disorders in youth have also included longitudinal follow-up that provide information on the predictors and consequences of mental disorders.17,19,21,35,67,68 Prospective Inhibitors,research,lifescience,medical follow-up of youth from many of the above studies have shown that child and adolescent mental disorders are related to a wide array of adverse outcomes.69,70 Risk factors for the development of mental disorders in children have been divided into child characteristics and those of his/her parents/family. Child characteristics include gender, age, ethnicity, physical health, cognitive and psychological function, pre- and perinatal exposures to illness, physical stress, alcohol, drugs, nutrition, Brefeldin_A infections and other environmental agents, and lifetime history of environmental exposures to toxins, stress, infections, social environment and stressful life events; family and parent characteristics including parental education, age, social class, employment, psychiatric and medical history, and family function, structure,7,10,19,71 and neighborhood and broader contextual influences on the health of children and their families.

In addition, the effects of drug noncompliance and EPS can both m

In addition, the effects of drug noncompliance and EPS can both mimic true treatment resistance.137,138 At least a 1- to 2-year course of persistent symptoms should also be considered as one of the criteria for treatment resistance in schizophrenia,

because of the waxing and waning course of this illness. The most widely accepted current criteria for treatment resistance in schizophrenia were first used by Kane et al.127 These criteria, modified for clinical use, are as follows: Persistent positive psychotic symptoms (item score ≥ 4) on Inhibitors,research,lifescience,medical at least two of four positive symptom items on the BPRS: hallucinatory behavior, suspiciousness, unusual thought content, or conceptual disorganization. Current presence of at least a moderately severe illness as rated by the total BPRS (score ≥45 on the 18item scale) and a score of ≥4 on the Clinical Global

Impression (CGI) scale. Persistence of illness: no period of good social and/or occupational functioning within the last Inhibitors,research,lifescience,medical 5 years. Drug-refractory condition defined as at least two periods of treatment in the preceding 5 years with appropriate doses of conventional or SGAs, each without clinically significant symptom relief. The rates for two retrospective drug trial failures have been found Inhibitors,research,lifescience,medical to be selleck inhibitor similar to the rates for three when screening for treatment resistance; this fact is now widely accepted.138 People Inhibitors,research,lifescience,medical not responsive to two adequate antipsychotic trials (one retrospective and one prospective) have less than a 7% chance of responding to another trial.139 The Food and Drug Administration (FDA) guidelines for clozapine, as reflected in the product labeling for clozapine,140 also states that people should fail to respond to two separate trials of antipsychotics, before being treated with clozapine. It is generally recognized that Inhibitors,research,lifescience,medical a 4- to 6-week period (rather than strictly a 6-wcck one) is adequate for a treatment trial of an antipsychotic.141 Dosages of >400 mg/day of chlorpromazine

have been shown to be adequate to block 80% to 90% of dopamine receptors (thought to be the target of this drug action).142 Higher doses produce no direct therapeutic benefit, even in patients not AG 14361 responsive to therapy, and do not have greater efficacy in acute treatment than lower doses.143-145 Therefore, two 4- to 6-weck trials of 400 to 600 mg/day chlorpromazine or a chlorpromazine equivalent are now accepted as a standard for an adequate trial.138,146 Until the arrival of standardized criteria for defining treatment resistance, research into the neurobiological nature of the problem had been scant.147 Recently, however, with the use of more objective criteria, some consistent findings have been seen. There is a relative paucity of data in this area and more research needs to be done.

1-3 The impetus to distinguish between the two types of dementia,

1-3 The impetus to distinguish between the two types of dementia, Alzheimer’s disease (AD) and the entity initially termed FTY720 Fingolimod multi-infarct dementia (MID) and later on vascular dementia (VD), had both scientific and pragmatic underpinning (the change from MID to VD was necessary, since the term MID did not cover the full range of cerebrovascular pathology). Reasoning for differentiation between AD and VD The scientific reasoning for the distinction between AD and VD was based on evidence collected Inhibitors,research,lifescience,medical during the 1970s

and 1980s, leading investigators to conclude that a vascular pathology was not the main underlying pathology for most demented individuals. First, many demented individuals had diffuse amyloid deposits or plaques and neurofibrillary tangles as the predominant postmortem pathology, with no or minimal vascular pathology or infarcts.1 Second, in some of these demented individuals with predominantly plaques and tangles, the counts of the cholinergic cells in the nucleus basalis of Meynert were diminished, as was the Inhibitors,research,lifescience,medical activity of the neurotransmitter acetylcholine in the cortex.4-8 Taken together, these findings convinced researchers that AD was a unique and discrete disease entity with well-defined

histology (presence of plaques and tangles) and neurochemistry (cholinergic Inhibitors,research,lifescience,medical deficiency), thus leading a sustainable hypothesis regarding its pathophysiology.9 On the other hand, as VD was conceptualized as a “matter of strokes large and small,”10 the Hachinski Ischemic Score was developed in order to differentiate it from AD. The scale is based on presence of risk factors for VD, such as hypertension, history of strokes, and evidence of associated atherosclerosis, and on the clinical characteristics of strokes (abrupt, onset, stepwise deterioration, fluctuating Inhibitors,research,lifescience,medical course, focal neurological signs, and symptoms). Additional support Inhibitors,research,lifescience,medical for a vascular origin of dementia according to the Hachinski Ischemic Score were the presence of nocturnal confusion, relative preservation of personality, depression, somatic complaints, and emotional incontinence.

The items making up the scale reflect the conceptualization of vascular risk factors as exclusively associated with brain infarcts, which, in turn, are responsible for the clinical manifestations of MID (and later VD). The pragmatic reasoning for the distinction between AD and VD was Carfilzomib the assumption in the late 1970s and early 1980s that specific treatments for AD exist, This assumption was based on the apparent finding that increasing cholinergic activity by pharmacological manipulations could improve symptoms in demented individuals.11-13 In order to increase the likelihood of demonstrating an effect for drugs enhancing cholinergic activities, it was believed to be essential to identify patients affected by a cholinergic deficit, ic, AD patients, and distinguish them from VD patients, who were not expected to benefit from cholinergic enhancement.

In an immunization study, discontinued due to serious side effect

In an immunization study, discontinued due to serious side effects, a reduction in t-tau in the CSF was observed in the group of antibody responders (development of a defined high antibody titer after vaccination) compared with the placebo group.127 Interestingly, MRI showed a decrease in whole brain volume in the responder group in this study.124 Amyloid reduction with consecutive changes in the CSF space

is being discussed as a cause, although this interpretation is controversial. Changes in the concentrations of the Aβ peptides in the CSF and plasma were reported after administration of a Inhibitors,research,lifescience,medical y-secretase inhibitor, a potential drug that may modify amyloid pathology.2 Furthermore, various combinations of neurochemical and neuroimaging biomarkers are currently used in several ongoing Inhibitors,research,lifescience,medical clinical trials on substances with potential disease-modifying properties (Table I). Conclusions and perspectives A number of neuroimaging candidate markers are promising, such

as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation and voxel-based morphometry, structural and effective connectivity using DTI, tractography, and fMRI. CSF Aβ42, BACE-1, total tau, and P-tau are substantially altered in MCI and clinical AD. Biomarker discovery through proteomic approaches requires further research. Despite the large number of promising results, biological markers of AD are Inhibitors,research,lifescience,medical at various stages of development and clinical evaluation (referred to as development stage I-IV), and have so far not generally been Inhibitors,research,lifescience,medical established

in clinical routine, In order to approach this goal, large-scale international controlled multicenter trials (such as the US, European, Australian, and Japanese ADNI, and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Also, biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification. Specific medium-term tasks Inhibitors,research,lifescience,medical in biomarker research include validation of the markers in autopsy-confirmed patient groups, determination of the benefit of biomarkers selleck compound in the risk stratification of clinical study populations using medico-economic models, and the controlled application of biomarkers in primary care. The aim selleck should be to have early diagnostic markers ready in clinical practice when disease-modifying treatments become available so that those patients who would benefit from these strategies can be identified and treated in time. To this end, there is a need for thorough and rigorous codevelopment of biological marker candidates with various functions and roles during all stages of drug development. This can only be achieved through planned synergistic collaboration between academic and industrial research partners.

No survival data were provided

Based on these data, LDP

No survival data were provided.

Based on these data, LDP appeared to be an appropriate oncologic surgical approach in select patients with cancer of the body/tail of pancreas. Laparoscopic pancreaticoduodenectomy (LPD) was first described by Gagner and Pomp in 1994 (60). Due to the complexity of the operation and lack of apparent advantages, reports regarding LPD contained case Inhibitors,research,lifescience,medical reports and small series. Series containing 10 or more successful LPD are listed in Table 1. While these reports demonstrated the safety and feasibility of performing LPD, larger prospective trials are needed to further define the advantage, if any, of LPD. Table 1 Select Literature on Laparoscopic PD Role of extended retroperitoneal lymphadenectomy Nodal status is a significant prognostic variable in pancreatic cancer. The number of nodes involved with metastases, the ratio of lymph node involvement, and the minimum number of lymph nodes examined had all been shown to have prognostic significance (67)-(69). Because of the importance of nodal staging, extended Inhibitors,research,lifescience,medical lymphadenectomy (EL) during pancreaticoduodenectomy was proposed to improve the surgical outcome of pancreatic cancer patients. The definition of EL is not uniform. Commonly EL referred to the dissection of additional

Inhibitors,research,lifescience,medical lymph nodes along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to the renal hila with circumferential clearance of the celiac trunk (70). While several groups from Japan

had reported favorable outcome following EL during pancreaticoduodenectomy (71)-(73), multiple randomized trials had not demonstrated an improvement in overall survival following EL (70),(74)-(76). Yeo et al also observed a significantly Inhibitors,research,lifescience,medical higher complication rate associated with the radical surgery group (43%) compared with the standard pancreaticoduodenectomy group Inhibitors,research,lifescience,medical (29%) (74). Higher rates of delayed gastric emptying and pancreatic fistula and longer hospital stay were observed in the radical surgery group. The higher selleck products morbidity associated with EL was also reported in a meta-analysis on standard versus radical pancreaticoduodenectomy Batimastat (77). The authors also did not find a difference in survival between the standard versus radical pancreaticoduodenectomy. Portal vein and superior mesenteric vein resection Because achieving an R0 resection had prognostic significance for patient outcome, vascular resection during PD had been evaluated. The great majority of vascular resection during PD involved portal vein and superior mesenteric vein resection and reconstruction. Yekebes et al reported equivalent perioperative morbidity and mortality between the standard PD group and the group with vascular resection (78). The median survival was 15 months in patients with histopathologic proven vascular invasion and 16 months in those without (P=0.86).

As a result, the PLA-MAA matrix maintained a tight interconnected

As a result, the PLA-MAA matrix maintained a tight interconnected networked structure and retarded the diffusion of MTX molecules. PLA imparted the nanoparticles with a certain degree of hydrophobicity, and its presence reduced the rate of matrix hydration by delaying the Idelalisib solubility penetration of H2O molecules. The combined hydration, relaxation, and degradation kinetics of PLA and MAA in the dissolution media resulted in prolonged MTX release for over 84 hours (Figure 10). The in vitro drug release data Inhibitors,research,lifescience,medical demonstrated that the PLA-MAA nanoparticulate system can provide

prolonged drug delivery (~80 hours) as compared to microparticles (12–25 hours) loaded with anticancer agents and prepared with different synthetic and natural polymer blends [45–47]. This prolonged rate of drug release allows the PLA-MAA system to be suitable for a nanoenclatherated

neuroerodible polymeric device Inhibitors,research,lifescience,medical wherein the nanoparticles can be assembled as a layer-by-layer process and provide programmable drug release of the loaded nanostructure as well as bioactives for therapeutic management of PCNSL. Figure 10 Release profile of MTX from an optimized PLA/MAA nanoparticle system with the highest drug incorporation efficiency. 3.7. Morphological Characterization of the PLA-MAA Inhibitors,research,lifescience,medical Nanoparticles SEM micrographs revealed the presence of nanoparticles that were pseudospherical in shape. At higher magnification, the surface morphology revealed a collapsed PLA-MAA matrix as a result of the curing process in the presence of 50% methanol (Figure 11(a)). SEM also showed polymer aggregates that were adsorbed onto a smooth surface. TEM images confirmed the formation of matrix-type nanoparticles with a partially formed core-shell structure represented as clear areas in the micrograph (Figure 11(b)). Figure 11 (a) SEM image showing the Inhibitors,research,lifescience,medical surface morphology of the optimized PLA/MAA nanoparticle formulation (x2500 magnification) and (b) TEM image of the optimized PLA/MAA nanoparticle formulation.

3.8. Assessment of the Thermal Properties of the PLA-MAA Nanoparticles The Inhibitors,research,lifescience,medical thermal stability of the PLA-MAA nanoparticles was investigated by temperature modulated DSC (TMDSC) with a temperature range of −35–230°C. With TMDSC, the effects of baseline slope and curvature for the analysed samples became reduced thereby increasing the sensitivity of the system. Overlapping events such as molecular Entinostat relaxation and glass transitions could be easily separated. With TMDSC, it was also possible to directly measure the Cp. TMDSC utilizes sinusoidal temperature modulations with constant heating and cooling rates typified by short small amplitudes that were able to unveil and distinguish important hidden, overlapping thermal events within the MTX-loaded PLA-MAA nanoparticle matrix. The theoretical Tg for PLA is recorded between 50 and 80°C while the Tm value is between 173 and 178°C [48]. MAA has a theoretical Tm value of 100°C and a Tg that ranges between 85 and 165°C [49].

The conditions are discussed in more detail in the following sect

The conditions are discussed in more detail in the following sections. Table II The genetic basis of conditions for which there is evidence that mutations give rise directly to intellectual disability. ATRX, alpha-thalassemia X-linked mental retardation syndrome; XLMR, X-linked mental retardation; IL-1, interleukin-1; IQ, intelligence … When we consider Inhibitors,research,lifescience,medical the pathogenesis of intellectual disability, it is important to bear in mind that the phenotype involves multiple domains of intellectual functioning,

often broadly divided into verbal and performance skills, but also encompassing capacities such as memory and attention, where performance is not traditionally seen as central to intellectual ability. Unfortunately, we do not know whether the domains that psychologists recognize correspond to the way genes operate, whether, for instance, Inhibitors,research,lifescience,medical verbal and performance skills can be separated at a genetic level. Information is lacking about genetic influences on the domains of both normal and abnormal intellectual functioning. Studies of the heritability of intelligence, a measure of the extent to which genes contribute to the variation in intellectual functioning in the population, have mostly been carried Inhibitors,research,lifescience,medical out on overall measures of cognitive function,

such as IQ, although more recent work on speech and language development is beginning to indicate that genetic effects that have more specific influences can be identified.15,16 Similarly,

there have been few detailed Inhibitors,research,lifescience,medical psychometric investigations of people with intellectual disability due to a specific genetic lesion, so we do not know whether cognitive functioning is abnormal over all domains or whether there are discrete abnormalities. In fact, as discussed later, there is some evidence in favor of the latter hypothesis. Genetic mapping Inhibitors,research,lifescience,medical techniques and molecular cloning have made it possible to investigate disorders where the relationship between intellectual disability and genetic defect Batimastat might be immediate. These are conditions where there are no noticeable alterations in brain structures and the cause of cognitive impairment is difficult to find. In general, this distinction is reflected in the division of MR into selleck chemical syndromic and nonsyndromic conditions. In syndromic MR, the phenotype includes additional physical abnormalities (such as facial dysmorphism or minor abnormalities of the hands and feet), while in nonsyndromic MR the only abnormality is cognitive impairment. It might appear that genetic lesions are directly responsible for intellectual disability more commonly in nonsyndromic than in syndromic conditions, but it should be borne in mind that, without an understanding of the pathogenesis, this is only an assumption.

1-11 The diagnosis of bipolar disorder is often

delayed,

1-11 The diagnosis of selleck chemical Palbociclib bipolar disorder is often

delayed, with the time between initial treatment seeking and the correct diagnosis often taking more than 10 years.12,13 The treatment and clinical implications of the failure to recognize bipolar disorder in depressed patients are significant, and include the underprescription of mood-stabilizing medications, an increased risk of rapid cycling, and increased costs of care.4,14-16 As a result of the potential morbidity associated with a delay in diagnosis, experts have called for improved recognition of bipolar disorder,1,6 and screening scales have been developed and recommended to facilitate Inhibitors,research,lifescience,medical the identification of bipolar disorder.17-19 Borderline personality disorder (BPD) is a common comorbidity in depressed patients that is also underdiagnosed.20 Compared with patients with major depressive disorder (MDD) without BPD, patients with MDD and BPD also have excess psychosocial morbidity.21,22 The recognition of BPD is clinically important because of the availability of specific psychotherapies Inhibitors,research,lifescience,medical that are effective23,24 and the possible overprescription of medications that have little benefit and carry the risk of medically significant side effects.25 Because of the potential treatment implications, it is

clinically important to recognize both bipolar disorder and BPD in patients seeking treatment Inhibitors,research,lifescience,medical for depression, and it is important to distinguish between the two. However, this presupposes that each is a valid diagnostic entity. During the past 20 years there have been increasing suggestions that BPD should be conceptualized as part of the spectrum of bipolar disorder. Advocates of the bipolar spectrum suggest that treatments that have been found effective in treating bipolar Inhibitors,research,lifescience,medical disorder should be used when treating patients with BPD because of its inclusion on the bipolar spectrum.6,26-28 Literature reviews considering whether BPD belongs to the bipolar

spectrum have reached differing conclusions. Smith et al29 suggested that a strong case could be made that a significant Inhibitors,research,lifescience,medical percentage of patients with BPD fall into the bipolar spectrum, and Belli et al30 concluded that the two disorders are closely linked in phenomenology and treatment response. Antoniadis et al31 and Coulston Dacomitinib et al32 did not draw a conclusion regarding BPD’s inclusion on the bipolar spectrum, whereas Paris et al33 and Dolan-Sewell et al34 concluded that empirical evidence did not support BPD’s link to the bipolar spectrum. Sripada and Silk,35 reviewing neuroimaging studies, noted that there were some areas of overlap and some differences between BPD and bipolar disorder. Some of the authors of these reviews noted that few studies have directly compared patients with bipolar disorder and BPD, and they called for such empirical data to help clarify the relationship between the two disorders.32,35 In the present review we focus on the most studied question on the relationship between BPD and bipolar disorder—their diagnostic concordance.

8 In a retro-spective analysis, rates of treatment-emergent mania

8 In a retro-spective analysis, rates of treatment-emergent mania were approximately twice as high when children who met the modified DSM-IV diagnostic criteria for PBD received antidepressants (44%) compared with those who received stimulants (18%).9 When stimulants and their potential effects on treatment-emergent manic symptoms were analyzed, adolescents with a history of treatment exposure prior to

the onset of PBD had an earlier age of onset than children without prior stimulant exposure.10 Furthermore, Inhibitors,research,lifescience,medical DelBello and coworkers, who carried out this study, showed that PBD-diagnoscd adolescents who had been receiving Inhibitors,research,lifescience,medical at least two different stimulant medications were younger at onset compared with patients who had received monotherapy stimulant treatment. This suggests a possible cumulative effect of stimulant-emergent manic states as a contextual risk factor for later-onset BD.10 This finding is PXD101 supported by other researchers, whose studies

indicate that prior treatment with antidepressants and/or stimulants was associated with earlier bipolar diagnosis and who compare these results to those of children Inhibitors,research,lifescience,medical who were never exposed to these medications.11 However, in view of the limited sample sizes and methodological limitations of these studies, these findings must be regarded as far from definite. Furthermore, the diagnosis of juvenile mania is often complicated by the clinical overlap of PBD symptoms and ADHD symptoms.12 However, there is also evidence not supporting this hypothesis.13,14 In view Inhibitors,research,lifescience,medical of the limited number of studies available, particularly on developmental aspects, it is essential to tackle the diagnostic challenges posed. If a patient with initial ADHD symptoms and later hypomanic PBD-related characteristics was not seen by his or her child and adolescent

psychiatrist during this hypomanic episode, Inhibitors,research,lifescience,medical the patient could be classified as an “ADHD only” or “pure ADHD” patient, because the comorbidity of PBD or the shift from ADHD to PBD symptoms would not be observed. Such cases could Carfilzomib not only lead to distorted diagnostic prevalence rates for PBD in clinical samples, but also to a camouflage of the ADHD/PBD comorbidity relationship. Further diagnostic factors such as biased symptom reporting by parents and carers, which dilute the observed effects, complicate matters further. In spite of the methodological hurdles hindering the feasibility of studies investigating the ADHD/PBD relationship, future longitudinal research is vital to clarify the complex diagnostic relationship between PBD and ADHD.

Subsequently, serum levels were assessed at Medtox Labs, USA, us

Subsequently, serum levels were assessed at Medtox Labs, USA, using a validated analytical method. Table 1 Properties of Risperidone PLGA microspheres. 3. Results and Discussion 3.1. Polymer Selection Properties of the four formulations used in this study are shown in Table 1. Formulations A and B were prepared with 50:50 PLGA at molecular weights 45 and 74kDa, respectively, while Formulations Inhibitors,research,lifescience,medical C and D were manufactured from 54 and 65kDa PLGA having a 75:25 lactide:glycolide ratio. Based on the molecular weight and copolymer ratio, Formulations A and B were expected to have a shorter duration of action while Formulations C and D would provide a more prolonged in vivo drug

release

profile due to a higher lactide content in the 75:25 copolymer. 3.1.1. Morphology of Risperidone Microspheres The scanning electron micrographs revealed a spherical shape with a smooth surface and homogeneous particle size distribution (Figure 1) that would be appropriate for subcutaneous administration Inhibitors,research,lifescience,medical to rats. Additionally, the microspheres could not be fractured suggesting that the interior of all four Inhibitors,research,lifescience,medical formulations was not hollow. When viewed at the same magnification (Figure 1), the particle size of Formulation A appeared marginally larger than Formulation B, while the particle size of Formulation C was slightly smaller than Formulation D. A glance at Table 1 confirms these observations as the mean particle sizes for Formulations A–D were 24.6, 18.9, 17.1, and 21.9µm, respectively. For dosage

forms like drug loaded microspheres, Inhibitors,research,lifescience,medical measurement of particle size is INCB-018424 important as it impacts “initial burst” release [49]. A smaller particle size confers a higher surface area to volume ratio to the dosage form. It follows that a larger surface area allows for rapid water incursion and consequently, faster dissolution of drug molecules that are associated with the outer surface or accessible pores. Inhibitors,research,lifescience,medical Hence, an initial burst is expected with smaller sized microspheres. Figure 1 SEMs of Risperidone PLGA microspheres. From literature, the particle size of the commercial long acting Risperidone microsphere formulation has been reported to be between 25 and 150μm [50], significantly larger than Formulations A, B, C, Carfilzomib and D. Hence, the SEM results in Figure 1 indicated that the release profiles from the four formulations would be vastly different from the marketed preparation. For instance, an “initial burst” of drug release was expected for all the formulations. Given that the particle sizes for Formulations A–D are quite similar overall, the extent of “initial burst” was expected to be broadly similar. 3.1.2. Bulk Density Bulk density values for PLGA microsphere formulations are routinely measured as they provide information on the porous network in these dosage forms.