三酸散的制备及苯甲酸和水杨酸的含量测定

目的：探讨三酸散的制备方法和建立 HPLC 法测定三酸散中苯甲酸和水杨酸的含量方法,为三酸散质量控制提供有效的分析手段。方法色谱柱：Eclipcy plus C18（250 mm ×4．6 mm,5μm）;流动相：甲醇—0．05 mol·mL －1磷酸二氢钾溶液（用磷酸调节 pH 值至4．0）（1∶1）;检测波长：232 nm;流速：1．0 mL·min －1;柱温：室温。结果苯甲酸和水杨酸的线性范围分别是5～30 mg·L －1和10～60 mg·L －1,回归方程分别是 A ＝109287C ＋37431（r ＝0．9943）和 A ＝63894C ＋4890．2（r ＝0．9956）。苯甲酸和水杨酸的平均回收率分别是100．2％（RSD ＝1．25％）和99．74％（RSD ＝1．43％）。结论该方法简单,结果准确可靠,可用于三酸散中苯甲酸和水杨酸的含量测定。     

气相色谱法测定聚乳酸乙醇酸中丙交酯的含量

目的建立气相色谱法测定聚乳酸乙醇酸中丙交酯的含量。方法采用气相色谱法,色谱柱为SE-54（30m×0．53mm×1．0μm）;柱温采用程序升温：先100℃保持2min,然后以10℃·min“增加到150℃并保持2min;分流比10：1;FID检测器;检测口240℃;进样口220℃;载气为氮气;流速8．0mL·min^-1;进样量0．5IxL。结果丙交酯25～2500mg·L^-1浓度范围内线性关系良好（r=0．9998）,对方法进行了回收率和精密度试验,样品平均回收率为97．2％。结论该方法准确、简便、专属性强,可以作为丙交酯含量分析法。     

高效液相色谱法测定氨甲环酸片的溶出度

目的建立HPLC法测定氨甲环酸片溶出度的检测方法。方法采用十八烷基硅烷键合硅胶柱（C18柱,Diamonsil,4．6mm×250mm,5μm）;流动相：0．23％十二烷基硫酸钠溶液（用磷酸调节pH至2．5）-甲醇（60：40）;检测波长：220nm;流速：1．0mL·min^-1;进样量：100扯L;柱温：30℃。结果氨甲环酸在29．76～357．12μg·mL^-1具有良好的线性关系（r=0．9999）;平均回收率为99．61％,RSD为0．45％（n=9）。结论本法简便、快速、准确、专属性好,为中国药典2010年版氨甲环酸片溶出度的修订提供了依据。     

HPLC法测定不同产地猪牙皂中刺囊酸的含量

目的：考察不同产地猪牙皂中刺囊酸的含量。方法：采用HPLC法,色谱柱：Agilent ZORBAX—C18柱（250mm×4．6mm,5μm）,流动相：乙腈-0．5％磷酸二氢钾溶液（72：28）（磷酸调pH3．2）,流速：1．0ml·min^-1,柱温：30℃,检测波长：215nm。结果：刺囊酸在0．0485～0．97mg·ml^-1（r=0．9997）浓度范围内有良好的线性关系,平均加样回收率为96．6％;RSD为1．46％。结论：该法简便,准确,重复性好,为猪牙皂的进一步开发和利用提供科学依据。     

60Co辐照对睾丸酮/乳酸-乙醇酸共聚物微球理化特性及体外释放的影响

目的 :睾丸酮 (T) /乳酸 -乙醇酸共聚物 (PLGA)微球6 0 Co辐照灭菌可行性研究。方法 :T/PLGA微球在6 0 Co源下 ,以 2 5kGy的剂量进行辐照 ,对微球辐照前后主药T、载体PLGA的理化特性和微球体外释药速率的变化进行比较 ,考察6 0 Co辐照对T/PLGA微球理化特性及药物体外释放的影响。结果 :6 0 Co辐照引起PLGA分子量一定程度的下降 ,但对T/PLGA微球的理化特性及体外释药速率没有影响。结论 :初步的可行性研究表明T/PLGA微球可用6 0 Co辐照灭菌     

乳酸羟乙醇酸共聚物微球中蛋白包封率的测定

目的:寻求一种合适的方法测定蛋白在乳酸羟乙醇酸共聚物(PLGA)微球中的包封率。方法:采用复乳 溶剂挥发法制备 BSA的PLGA微球,应用考马斯亮蓝法测定总蛋白浓度,根据文献报道的7种不同方法进行包封率测定。结果:不同的测定方法对 PLGA微球中真实的药物包封率的反映程度不同,相互间差异很大。结论:以水解法测定BSA在PLGA微球中包封率的方法提取 最完全。水解法中,又以乙腈作溶剂、再用氢氧化钠水解两步提取法最为简便、快速、准确。     

RP-HPLC法测定人血浆中富马酸比索洛尔的浓度

以催醒胺为内标．建立TRP－HPLC法规定人血浆中富马酸比索洛尔的浓度。色谱柱采用Nova－pakC18分析柱,流动相为己腈-甲醇-磷酸（0．09mol／L）-水（34：10：6：50v／v）,荧光检测波长232／300nm（Ex／Em）。血浆样品经碱化后乙酸提取可获得良好分离,血药浓度在4～128ng／ml范围内呈线性关系,相关系数0．9998,最低检测浓度为2ng／ml。生物样品的平均方法回收率98．34％～105．43％,平均提取回收率75．01％～97．48％,日内日间精密度RSD0．73％～9．06％。     

UPLC 法测定白花蛇舌草注射液中对香豆酸的含量

目的：建立白花蛇舌草注射液中对香豆酸的含量测定方法。方法采用 ACQUITY UPLC BEH C18柱（2．1 mm ×50 mm,1．7μm）为色谱柱,以甲醇—0．3％醋酸溶液为流动相,梯度洗脱,流速为0．4 mL·min －1,检测波长为308 nm。结果对香豆酸进样量在1．68～67．12 ng 范围内与峰面积线性关系良好,r ＝0．99999,平均加样回收率为99．8％,RSD 为0．7％。测得16批样品中对香豆酸的平均含量为0．204 g·L －1。结论该方法简便准确,快速可靠,能够用于白花蛇舌草注射液的含量测定和质量控制。     

气相色谱法测定聚维酮碘溶液中乙醇和乙酸的残留量

目的建立毛细管气相色谱法测定聚维酮碘溶液中乙醇和乙酸的残留量。方法采用毛细管气相色谱法,色谱柱为Agilent J＆W DB-624（30m×0．320mm,1．80ttm）;柱温采用程序升温;进样口温度为200℃;检测器温度为240℃;载气为高纯氮;检测器为FID。结果乙醇和乙酸的质量浓度（p）在0．20032～4．0064g·L-1时与其峰面积（A）之间呈良好线性关系,r分别为1．0000．0．9998。高、中、低3种浓度下的日内和日间精密度良好,RSD为0．62％～2．88％。乙醇和乙酸的检测限分别为0．18、4．68mg·L-1。乙醇和乙酸加样回收率分别为99．70％、99．00％（n=6）,RSD分别为0．59％、1．05％。结论本法简便、快捷、灵敏度高,适用于聚维酮碘溶液中乙醇和乙酸残留量的测定。     

HPLC法测定注射用氨甲环酸中氨甲环酸的含量

目的建立注射用氨甲环酸中氨甲环酸含量的测定方法。方法高效液相色谱法。采用watersSunFireC18柱（4．6mm×150mm,3．5μm）,流动相为O．23％十二烷基硫酸钠溶液（取磷酸二氢钠18．3g,加水B00mL溶解,加三乙胺8．3mL混匀后,再加十二烷基硫酸钠2·3g,振摇使溶解。用磷酸调节pH至2．5,加水至1000mL,摇匀）-甲醇（70：30）;检测波长为210hm。结果氨甲环酸在0．5206-2．6031mg·mL-1范围内线性关系良好,r=1．0000;平均加样回收率为100．7％,RSD为0．5％（n=9）。结论此方法简便、准确,重现性好,可用于测定注射用氨甲环酸中氨甲环酸的含量。     

Determination of water-soluble acid distribution in poly(lactide-co-glycolide)

Determination of the kinetics of water-soluble degradation products inside poly(lactide-co-glycolide) (PLGA) delivery systems during polymer degradation is important to evaluate the polymer microclimate conditions, particularly microclimate pH changes for optimization of encapsulated drug stability. A pre-derivatization high-performance liquid chromatography (HPLC) method was developed for separation and quantification of water-soluble acid impurities and degradation products in PLGA. Thin PLGA films (approximately 200 microm) were incubated in PBS/0.02% Tween 80, pH 7.4, for 6 weeks. Water-soluble monomers and oligomers were obtained from polymer films after repeated CHCl(3)/H(2)O extraction and then derivatized into bromophenacyl esters. With the common chromophore, the esters were separated and quantified by HPLC with increased ultraviolet (UV) sensitivity at 254 nm. The total amount of water-soluble acids in the extract was validated by potentiometric titration with tetrabutyl ammonium hydroxide. During the first 3 weeks of incubation of PLGA 50:50 (inherent viscosity = 0.63 dL/g), the principal water-soluble acids in the polymer were glycolic, lactic, and lactoyllactic acids, and an unknown oligomer. After 4 weeks of incubation, a large fraction of higher molecular weight oligomers was observed. Pre-derivatization HPLC can be used to accurately measure water-soluble acid distribution, and may be invaluable to examine the degradation behavior of PLGAs, including the underlying mechanism of polymer microclimate pH development.     

Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy

PURPOSE: The acidic microclimate pH (micropH) distribution inside poly(lactic-co-glycolic acid) (PLGA) microspheres was monitored quantitatively as a function of several formulation variables. METHODS: A ratiometric method by confocal laser scanning microscopy with Lysosensor yellow/blue dextran was adapted from those previously reported, and micropH distribution kinetics inside microspheres was examined during incubation under physiologic conditions for 4 weeks. Effects of PLGA molecular weight (MW) and lactic/glycolic acid ratio, microspheres size and preparation method, and polymer blending with poly(ethylene glycol) (PEG) were evaluated. RESULTS: micropH kinetics was accurately sensed over a broadly acidic range (2.8 < micropH < 5.8) and was more acidic and variable inside PLGA with lower MW and lactic/glycolic acid ratio. Lower micropH was found in larger microspheres of lower MW polymers, but size effects for lactic-rich polymers were insignificant during 4 weeks. Microspheres prepared by the oil-in-oil emulsion method were less acidic than those prepared by double emulsion, and blending PLGA 50/50 with 20% PEG increased micropH significantly (micropH > 5 throughout incubation). CONCLUSIONS: Coupling this method with that previously developed (SNARF-1 dextran for micropH 5.8-8.0) should provide microclimate pH mapping over the entire useful pH range (2.8-8.0) for optimization of PLGA delivery of pH-sensitive bioactive substances.     

Peptide Acylation by Poly(α-Hydroxy Esters)

Purpose. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres were investigated concerning the possible acylation of incorporated peptides. Methods. Atrial natriuretic peptide (ANP) and salmon calcitonin (sCT) were encapsulated into PLA and PLGA microspheres. Peptide integrity was monitored by HPLC-MS analysis during microsphere degradation for four weeks. sCT fragmentation with endoproteinase Glu-C was used for identifying modified amino acids. Peptide stability in lactic acid solutions was investigated to elucidate possible mechanisms for preventing peptide acylation. Results. Both peptides were acylated by lactic and glycolic acid units inside degrading microspheres in a time-dependent manner. After 21 days, 60% ANP and 7% sCT inside PLA microspheres were acylated. Fragmentation of sCT with endoproteinase Glu-C revealed that besides the N-terminal amine group, lysine, tyrosine or serine are further possible targets to acylation. Stability studies of the peptides in lactic acid solutions suggest that oligomers are the major acylation source and that lower oligomer concentration and higher pH substantially decreased the reaction velocity. Conclusions. The use of PLA and PLGA for drug delivery needs substantially more circumspection. As, according to FDA standards, the potential hazards of peptide acylation products need to be assessed, our findings may have significant implications for products already on the market. Techniques to minimize the acylation reaction are suggested.     

Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres

This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55–95 µm and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37°C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37°C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.     

Negligible penetration of incidental amounts of alpha-hydroxy acid from rinse-off personal care products in human skin using an in vitro static diffusion cell model

Alpha-hydroxy acids (AHAs), primarily glycolic and lactic acids, are widely used in cosmetics to alleviate dyspigmentation, photodamage, and other aging skin conditions and as pH adjusters. Glycolic acid reportedly enhances skin damage after repeated ultraviolet light exposure, e.g., increased sunburn cell formation. This study assessed potential in vitro skin penetration of lactic acid and malic acid incorporated into rinse-off personal care products, compared with rinse-off and leave-on exposures to glycolic acid (10%, pH 3.5) in a reference lotion. Radiolabeled AHA-fortified shampoo, conditioner, and lotion were evenly applied as single doses to human epidermal membranes mounted in static diffusion cells (not occluded). Exposures were 1–3 min (rinse-off) or 24 h (leave-on). Epidermal penetration of malic acid and lactic acid from the rinse-off shampoo and conditioner, respectively, was negligible, with >99% removed by rinsing, a negligible portion remaining in the stratum corneum (?0.15%), and even less penetrating into the viable epidermis (?0.04%). Glycolic acid penetration from the leave-on reference lotion was 1.42 μg equiv./cm²/h, with total absorbable dose recovery (receptor fluid plus epidermis) of 2.51%, compared to 0.009%, 0.003%, and 0.04% for the rinse-off reference lotion, shampoo (malic acid), and conditioner (lactic acid) exposures, respectively. Dermal penetration of AHAs into human skin is pH-, concentration-, and time-dependent. Alpha-hydroxy acids in rinse-off shampoos and conditioners are almost entirely removed from the skin within minutes by rinsing (resulting in negligible epidermal penetration). This suggests that ultraviolet radiation-induced skin effects of AHA-containing rinse-off products are negligible.     

建立UPLC法测定复方氨基酸胶囊(9-5)中氨基酸的含量

目的通过优化色谱条件建立UPLC法测定复方氨基酸胶囊(9-5)中氨基酸的含量。方法以9种氨基酸对照为外标物,异硫氰酸苯酯为柱前衍生剂,采用ACQUITY UPLCBEH C_(18)(2.1 mm×100 mm,1.7μm)柱,流动相A为0.1 mol/L的醋酸钠溶液(用冰醋酸调整pH至6.50)-乙腈(93∶7),流动相B为乙腈-水(4∶1),检测波长254 nm,流速为0.45 mL/min,柱温36℃。结果复方氨基酸胶囊(9-5)中9种氨基酸出峰时间与对照品出峰时间一致,其他物质无干扰;仪器精密度RSD为0.5%~1.2%,中间精密度RSD为1.3%~1.9%;各氨基酸的溶液浓度与其峰面积线性关系良好(r≥0.999),溶液稳定性RSD为0.6%~1.8%,各氨基酸的平均回收率在95.0%~105.0%之间。含量测定方法比对实验中UPLC法与HPLC法分析结果无明显差异,分析速度明显提高。结论建立的UPLC法高效,快速,灵敏,准确,可用于测定复方氨基酸胶囊(9-5)中氨基酸的含量。     

Comparative Pharmacokinetics and Biodistribution of Etoposide in a Polymer Dosage Form and as Free Drug Substance

Pharmaceutical Chemistry Journal - A polymer dosage form of etoposide (PFE) was obtained as submicron particles based on the copolymer of lactic and glycolic acids (PLGA). Pharmacokinetics and...     

Physicochemical and Biological Properties of a Nanostructured IR-Photosensitizer Based on Dipropoxybacteriopurpurinimide

Pharmaceutical Chemistry Journal - The production technology for nanoparticles based on a copolymer of lactic and glycolic acids (PLGA) containing dipropoxybacteriopurpurinimide (DPBPI) and...     

Biodegradable tablets having a matrix of low molecular weight poly-L-lactic acid and poly-D,L-lactic acid

Biodegradable Homo- and Copolymers of lactic and glycolic acids have been used for manufacture of microparticles and matrix implants^1,5). To ensure sufficient hydrolytic matrix stability lactic acids of high and medium degree of polymerization have been used. The manufacture of poly lactic acid tablets with an average molecular weight of 25000 and 6000 was reported recently, after finishing the following study²).     

Formulation and evaluation of butenafine loaded PLGA-nanoparticulate laden chitosan nano gel

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BT-NPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection.