The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were a...The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.展开更多
The potential benefits of pyrotinib for patients with trastuzumab-insensitive,HER2-positive early-stage breast cancer remain unclear.This prospective,multicentre,response-adapted study evaluated the efficacy and safet...The potential benefits of pyrotinib for patients with trastuzumab-insensitive,HER2-positive early-stage breast cancer remain unclear.This prospective,multicentre,response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab(TCbH).Early response was assessed using magnetic resonance imaging(MRI)after two cycles of treatment.Patients showing poor response,as defined by RECIST 1.1,could opt to receive additional pyrotinib or continue standard therapy.The primary endpoint was the total pathological complete response(tpCR;ypT0/isN0)rate.Of the 129 patients enroled,62(48.1%)were identified as MRI-responders(cohort A),26 non-responders continued with four more cycles of TCbH(cohort B),and 41 nonresponders received additional pyrotinib(cohort C).The tpCR rate was 30.6%(95%CI:20.6–43.0%)in cohort A,15.4%(95%CI:6.2–33.5%)in cohort B,and 29.3%(95%CI:17.6–44.5%)in cohort C.Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C(odds ratio=1.04,95%CI:0.40–2.70).No new adverse events were observed with the addition of pyrotinib.Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation(36.0%vs.60.0%,P=0.08).These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy.Further investigation is warranted to identify biomarkers predicting patients’benefit from the addition of pyrotinib.展开更多
文摘The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.
基金funded by the Clinical Research Center of Shandong University(Grant No.2020SDUCRCA003)the National Natural Science Foundation of China(Grant Nos.82273701 and 82072914)the Fundamental Research Funds for the Central Universities(Grant No.2022JC009).
文摘The potential benefits of pyrotinib for patients with trastuzumab-insensitive,HER2-positive early-stage breast cancer remain unclear.This prospective,multicentre,response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab(TCbH).Early response was assessed using magnetic resonance imaging(MRI)after two cycles of treatment.Patients showing poor response,as defined by RECIST 1.1,could opt to receive additional pyrotinib or continue standard therapy.The primary endpoint was the total pathological complete response(tpCR;ypT0/isN0)rate.Of the 129 patients enroled,62(48.1%)were identified as MRI-responders(cohort A),26 non-responders continued with four more cycles of TCbH(cohort B),and 41 nonresponders received additional pyrotinib(cohort C).The tpCR rate was 30.6%(95%CI:20.6–43.0%)in cohort A,15.4%(95%CI:6.2–33.5%)in cohort B,and 29.3%(95%CI:17.6–44.5%)in cohort C.Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C(odds ratio=1.04,95%CI:0.40–2.70).No new adverse events were observed with the addition of pyrotinib.Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation(36.0%vs.60.0%,P=0.08).These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy.Further investigation is warranted to identify biomarkers predicting patients’benefit from the addition of pyrotinib.
