Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Efficacy and Tolerability of Long-Acting Injectable Formulation of Nalmefene (Nalmefene Consta 393.1 mg) for Opioid Relapse Prevention: A Multicentre, Open-Label, Randomised Controlled Trial

Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.

A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Long-Acting Injectable Formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for Cocaine Relapse Prevention

Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.

Optimal needle insertion length for intramuscular injection of risperidone long-acting injectable (RLAI)

Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.

Effects of Depth of Needle Insertion with Risperidone Long-Acting Injectable in Persons with Schizophrenia: A Randomized Double-Blind Study

In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. Few clinical studies were done to evaluate the depth of needle length insertion reaching the intended gluteal muscle. The aim of this study was to evaluate the suitable depth of injecting RLAI. Twenty-six patients with schizophrenia were treated with RLAI, and randomly divided into two groups: 50 mm needle inserted group (Group-D, deep insertion, n = 13) and 20 mm needle insertion group (Group-S, shallow insertion, n = 13). For Group-S, the needle length was marked with a spacer at exactly 20 mm. Injections were performed by the psychiatrist or nurse, alternating between the two gluteal sites by double-cross method every two weeks. Clinical psychotic symptoms and injection site reactions were recorded throughout the study period. Experienced psychologists who were blinded from the needle-length experimental variable evaluated patients’ psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS) every two weeks. The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks;comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, injection site skin reactions of subjects in both groups. However, in Group-D, injection site adverse reactions were confirmed in two subjects (15%). In Group-S, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion using both depth, it was concluded that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.

Long-Term Clinical Outcome of Patients Using Risperidone Long-Acting Injectable: The Romanian e-STAR Database

The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.

Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis.Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro.In a collagen-induced arthritis rat model,we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection.Such prodrug demonstrated long-acting anti-arthritis effects with good safety.Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.

A Novel RP-HPLC Method for Estimating Fulvestrant, Benzoyl Alcohol, and Benzyl Benzoate in Injection Formulation

For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.

A novel formulation of bupivacaine-encapsulated PLGA nanoparticles in peripheral analgesia

Bupivacaine encapsulated poly(lactidecoglycolide)nanoparticles is a novel formulation of extended-release of bupivacaine in poly(lactidecoglycolide)matrix.We evaluated the efficacy and safety of bupivacaine nanoparticles in peripheral analgesia via behavior tests,electrophysiological recordings,pharmacokinetic analysis,and pathology staining by employing the models of uninjured rats and mice.Nanoparticles injection increased the pain thresholds of rats and mice for 21 days.

注射用环糊精包合物研究进展

传统注射剂中对于难溶性药物采用的增溶手段多为添加有机助溶剂或表面活性剂,其刺激性易导致疼痛、炎症等多种不良反应。环糊精(cyclodextrin,CD)是一种具有空穴的环状低聚糖,部分天然环糊精及其衍生物具有良好的水溶性和生物相容性,可以通过包合作用增加难溶性药物的溶解度及稳定性,且降低对注射部位的刺激,是注射剂中增溶剂的更优选择。本文对环糊精在已上市注射剂产品中的应用及其发展前景进行综述,为环糊精在注射剂中更广泛的应用发展提供参考。

Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. Methods Fifteen patients with TSH-secreting pituitary adenomas （8 men and 7 women）, who previously underwent incomplete surgical resection and/or adjuvant radiotherapy （n=12） and failure of octreotide treatment （n=15）, followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables. Results After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine （FT4） （（16.02±1.72） pmol/L） and free triiodothyronine （FT3） （（2.87±0.43） pmol/L） levels of 15 patients significantly decreased compared with those after octreotide-treatment （FT4, （35.36±7.42） pmol/L, P 〈0.001; FT3, （17.85±7.22） pmol/L, P 〈0.001）. Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment （（0.72±0.21） mUlL） and were significantly lower than the pretreatment value （（5.27±1.04） mUlL, P 〈0.001）, post-surgery value （（3.37±0.31） mU/L, P 〈0.001） and post-octreotide-treatment value （（4.52±0.41） mU/L, P 〈0.001）. In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis. Conclusion The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.

Pharmacokinetics,pharmacodynamics and safety of a single-dose long-acting Risperidone injection in Chinese patients with schizophrenia

In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.

全因子实验设计筛选紫杉醇注射液处方工艺及其表征

目的筛选紫杉醇注射液的最优处方工艺,并对其进行表征。方法根据参比制剂的处方组成,结合可行的放大生产工艺,采用Minitab软件对辅料的处方用量进行优化,以有关物质作为考察指标,进行全因子实验设计与分析。对紫杉醇注射液的粒径及粒径分布、Zeta电位进行表征。结果优化的处方工艺:水分控制为≤0.3%,处方中不加入枸橼酸,残氧量控制为≤6%。能够确保优化处方工艺制备的紫杉醇注射液有关物质控制为≤0.4%。优化后处方工艺制备的样品与参比制剂表征一致。结论筛选的紫杉醇注射液处方合理,工艺可行。

“注干液剂”的概念及实践

在对各种树木茎干施药技术研究的基础上，提出了“注干液剂”的概念，并介绍了其在生产实际中的应用。

14%吡虫啉·敌敌畏注干液剂防治柳树天牛技术研究

利用14%吡虫啉.敌敌畏注干液剂、4.15%吡虫啉.阿维菌素注干液剂、4.5%吡虫啉注干液剂、10%啶虫脒注干液剂和30%敌畏.氧乐注干液剂等5种药剂进行了树干注射防治危害柳树的光肩星天牛(Anop lophora g labrip enn is(M otschu lsky))试验,并研究了14%吡虫啉.敌敌畏注干液剂田间防治光肩星天牛的使用技术。结果表明,供试的5种注干药剂对光肩星天牛幼虫均有一定的防治作用,其中14%吡虫啉.敌敌畏注干液剂防效最好。14%吡虫啉.敌敌畏注干液剂以1.0 mL/cm树干胸径注药量对天牛幼虫的防效可达90.7%,优于对照药剂30%敌畏.氧乐注干液剂。利用14%吡虫啉.敌敌畏注干液剂林间防治天牛时,当幼虫虫口密度低于1.15头/株时,1年注药1次;虫口密度约为5头/株时,1年注药2次;虫口密度约为12头/株时,两年注药3次,可将虫口密度控制到0.15头/株以下,有效控制天牛的危害。

处方因素对依达拉奉注射剂稳定性的影响

目的:研究处方的组成和制备工艺对依达拉奉注射剂稳定性的影响。方法:采用高效液相色谱法测定注射剂的含量和有关物质,考察pH值、抗氧剂、助溶剂和制备工艺对注射剂含量的影响。结果:加入抗氧剂、助溶剂、将溶液pH调节为3.0～4.5可增加依达拉奉注射液的稳定性。结论:改变处方和工艺可以获得稳定的依达拉奉注射剂。

溴吡斯的明注射液的制备及其含量测定

目的:研究溴吡斯的明注射液的处方及制备工艺,并建立高效液相色谱法检测溴吡斯的明注射液的含量。方法:以稳定性为指标,筛选处方。采用十八烷基硅烷键合硅胶色谱法检测溴吡斯的明注射液的含量。结果:本品最适pH值为4.5～5.5。溴吡斯的明在150～350μg.mL-1范围内具有较好的线性关系,相关系数r=0.999 9,平均回收率为(99.79±0.69)%,精密度及稳定性均较好。制备的3批样品的含量分别为100.12%,99.98%和99.99%。结论:本品处方设计合理,工艺可行,质量稳定。所建立的高效液相色谱法可用于溴吡斯的明注射液含量的测定,且方法简便、准确。

土霉素注射液在猪体内药代动力学比较

对长效土霉素注射液进行了猪体内药代动力学的比较研究。试验将三种产品（Ａ、Ｂ、Ｃ）分别一次肌肉注射猪３头，剂量２０ｍｇ／ｋｇ。结果表明，消除半衰期以产品Ｂ最长，血药峰浓度以产品Ｂ最高，达到峰浓度时间以产品Ａ最慢，药时曲线下面积以产品Ｂ最大，２４小时血药浓度以产品Ｂ最高，４８小时血药浓度以产品Ｃ最低。以血浆土霉素浓度０．５μｇ／ｍｌ为最小有效浓度，产品Ａ和Ｂ能够维持有效血药浓度２４小时，产品Ｃ仅能够维持有效血药浓度１２小时。

维生素C棕榈酸酯泡囊作为维A酸载体的研究

采用溶剂注入法制备并优化了维A酸维生素C棕榈酸酯泡囊配方。所得制品呈球形,包封率达90%。4℃避光贮存6个月,含量和包封率无明显下降。

蟾酥脂质微球注射液的制备及其灭菌稳定性

目的研究蟾酥脂质微球注射液的处方工艺并考察制剂的灭菌稳定性。方法采用两级高压均质法制备蟾酥脂质微球注射液,分别考察油相组成、乳化剂用量、pH、灭菌方式对制剂灭菌稳定性的影响。结果采用质量分数为10.00%的油相[注射用中链脂肪酸甘油酯(MCT)与注射用大豆油(LCT)等比例混合],质量分数为1.20%的豆磷脂,质量分数为0.06%的油酸钠,均质前调节pH6.5,采用100℃旋转水浴灭菌30 min,制备所得的蟾酥脂质微球注射液在灭菌后仍保持良好的物理化学稳定性。结论粒子界面荷电性、空间位阻作用、pH、灭菌方式是影响蟾酥脂质微球注射液的物理化学稳定性的重要因素。