Evaluation of Different Screening Methods to Understand the Dissolution Behaviors of Amorphous Solid Dispersions.

Evaluation of different screening methods to understand the dissolution behaviors of amorphous solid dispersions.

Drug Dev Ind Pharm. 2013 Jun 26;
Lee TW, Boersen NA, Yang G, Hui HW

Abstract Objective: The objectives of the current study were to understand the dissolution behaviors of amorphous solid dispersions (ASD) using different screening methods and their correlation to the dissolution of formulated products. Materials and methods: A poorly soluble compound, compound E, was used as a model compound. ASDs were prepared with HPMC, Kollidon VA64 and Eudragit EPO using hot-melt extrusion. Different techniques including precipitation, powder, capsule and compact dissolution and the dissolution of formulated products were conducted in USP simulated gastric fluid using a USP II dissolution apparatus. Results and discussions: It was found that a precipitation study could generally predict powder, capsule and compact dissolution. Yet, it was recommended to run the dissolution at a higher paddle speed or for a longer duration to improve the predictability. It was also recommended to run powder, capsule and compact dissolution at both slow and high speeds to gain insights into wetting, dispersion and the dissolution of a system. Sometimes, capsule or compact dissolution could not be predicted by precipitation or powder dissolution due to plug formation. In this case, properly designed dosage forms were needed to break up this plug to optimize the dissolution profiles. On the contrary, formulations and dissolution conditions would have minimal effects on the dissolution profiles of a fast-dissolving solid dispersion. Conclusions: Different techniques are available to select the right polymers to optimize dissolution behaviors. However, it is important to understand the merits and limitations of each technique in order to optimize the formulations for amorphous solid dispersions. HubMed – drug


Novel application of polioviral capsid: development of a potent and prolonged oral calcitonin using polioviral binding ligand and Tat peptide.

Drug Dev Ind Pharm. 2013 Jun 26;
Manosroi J, Lohcharoenkal W, Götz F, Werner RG, Manosroi W, Manosroi A

Abstract Context: Poor absorption and proteolytic degradation are major obstacles of orally administered peptide drugs including calcitonin. Cell penetrating peptides (CPPs) and receptor binding ligands are interesting tools for the application in the delivery of these drugs. Objective: To investigate the enhancements of in vitro and in vivo salmon calcitonin (sCT) activity by Tat, a trans-activating transcriptional peptide and VP1 peptide (V) from polioviral capsid. Materials and methods: Tat/sCT, V/sCT and V/Tat/sCT mixtures at various molar ratios were prepared and investigated for in vitro and in vivo activities of sCT. Results: Tat could increase in vitro sCT activity both in colon adenocarcinoma (HT-29) and mouth epidermal carcinoma (KB) cells. V/sCT (6:1) showed significant increase of intracellular calcium in HT-29 cells. V/Tat/sCT (6:1:1) gave highest increase of intracellular calcium in both cells. Oral administered Tat/sCT (1:1) showed comparable hypocalcemic effect to sCT injection with prolonged action. V/Tat/sCT (6:1:1) demonstrated hypocalcemic effect at 12?h after administration but no hypocalcemic effect was observed from V/sCT. Discussion: Positive charge from Tat might facilitate sCT uptake and absorption. Increasing of intracellular calcium in HT-29 cells by V but lacking of hypocalcemic effect from V/sCT in mice indicated the ligand-receptor mediated delivery of sCT by the interaction between V and PVR. Conclusion: Potential application of V and Tat in oral calcitonin delivery system was demonstrated. Further study in a proper PVR bearing host is still needed to provide more useful information for the application of V in the development of drug delivery systems. HubMed – drug


Physician Allocation of Medicare Resources for Patients with Advanced Cancer.

J Palliat Med. 2013 Jun 26;
Rocke DJ, Lee WT, Beumer HW, Taylor DH, Schulz K, Thomas S, Puscas L

Abstract Background: Little is known about what patients and physicians value in end-of-life care, or how these groups would craft a health plan for those with advanced cancer. Objective: The study objective was to assess how otolaryngology, head and neck surgery (OHNS) physicians would structure a Medicare benefit plan for patients with advanced cancer, and to compare this with cancer patient and cancer patient caregiver preferences. Design: OHNS physicians used an online version of a validated tool for assessing preferences for health plans in the setting of limited resources. These data were compared to cancer patient and caregiver preferences. Setting and participants: OHNS physicians nationwide were assessed with comparison to similar data obtained in a separate study of cancer patients and their caregivers treated at Duke University Medical Center. Results: Otolaryngology physicians (n=767) completed the online assessment and this was compared with data from 146 patients and 114 caregivers. OHNS physician allocations differed significantly in 14 of the 15 benefit categories when compared with patients and caregivers. Physicians elected more coverage in the Advice, Emotional Care, Palliative Care, and Treatment for Cancer benefit categories. Patients and their caregivers elected more coverage in the Cash, Complementary Care, Cosmetic Care, Dental and Vision, Drug Coverage, Home Improvement, House Calls, Nursing Facility, Other Medical Care, and Primary Care benefit categories. Conclusions: Otolaryngology physicians have significantly different values in end-of-life care than cancer patients and their caregivers. This information is important for efficient allocation of scarce Medicare resources and for effective end-of-life discussions, both of which are key for developing appropriate health policy. HubMed – drug


Off-Label and Off-NCCN Guidelines Uses of Antineoplastic Drugs in China.

Iran J Public Health. 2013; 42(5): 472-479
Wang W, Zhu M, Guo D, Chen C, Wang D, Pei F, Ma L

To evaluate off-label and off-NCCN guidelines uses of antineoplastic drugs in a major Chinese hospital.Totally 1122 patients were selected from July to December 2011. Then, the off-label and off-NCCN guidelines uses of antineoplastic drugs were analyzed.In 798 of 1122 patients (71.12%), drugs were used for off-label. In 317 of 1122 patients (28.25%), the drugs were prescribed for off-label and off-NCCN guidelines. 2591 medical orders for 1122 patients, 1051/2591 (40.56%) medical orders were off-label; 445/2591(17.17%) medical orders were off-label and off-NCCN guidelines. In 445 off-label and off-NCCN medical orders, 399 (89.66%) were unapproved indications, 38 (8.54%) were unapproved drug concentration and 12 (2.70%) were unapproved route of administration. Percentage of off-label and off-NCCN guidelines drug uses in male was higher than that in female (21.92% vs. 11.39%, P<0.01). Compared with other lines of treatment, percentage of off-label and off-NCCN guidelines drug uses in postoperative adjuvant was the smallest (P<0.01) and percentage in three or multi-line treatments was the highest (P<0.01). The pancreatic cancer possessed the highest percentage (38.74%) of off-label and off-NCCN guidelines drug uses among all types of cancer (P<0.01).Off-label uses of antineoplastic drugs are generally common in China hospitals based on NCCN guidelines. The fact suggests that anti-tumor treatment was relatively standard in China. Off-label and off-NCCN guidelines drug uses were mainly for individual treatment. Doctors should fully consider the adverse drug reaction, contraindication, cautions and increase the drug security monitoring. Uncorrected drug concentration should be avoided for drug risk. HubMed – drug