明胶冻力对尼莫地平软胶囊溶出稳定性的影响

将不同来源和冻力差异的明胶制成软胶囊和胶皮后,通过测定软胶囊的溶出度、胶皮的平衡膨胀量和氨基酸残基含量,考察软胶囊的稳定性,对明胶的组分进行分离和测定,考察其交联反应活性.结果显示,加速条件下放置90 d后,软胶囊的溶出度显著降低(P<0.05),且明胶冻力越高,溶出度越低,胶皮的平衡膨胀量和ω-氨基酸残基含量亦有相同变化.DSC图谱显示,考察后样品囊壳吸热峰向温度较高的区域偏移,且明胶冻力越高,偏移幅度越大.明胶分子主要含有α、β和γ等组分,其中α组分与明胶的冻力有良好的相关性,各组分的交联反应活性依次为α>β>γ.     

麻黄软胶囊的溶出稳定性及影响因素考察

目的：考察中药麻黄软胶囊的溶出稳定性及影响因素,探讨中药软胶囊溶出迟缓机制。方法：采用加速试验,评价麻黄软胶囊的溶出稳定性;以平衡溶胀量和ε-氨基酸残基含量为指标,评价明胶囊壳的交联程度;应用红外光谱和醛类专属反应,鉴定麻黄提取物中醛类成分,并测定其含量。结果：在加速试验条件下（40℃,75％相对湿度）,放置30天后,明胶囊壳的平衡溶胀量和ε-氨基酸残基含量均显著下降（P〈0．01）,其交联度显著增加（P〈0．01）;放置60天后,麻黄软胶囊溶出度显著下降（P〈0．01）。环境因素（高温／高湿）、溶媒介质（聚乙二醇）和药物成分（麻黄提取物）均可导致明胶交联度显著提高（P〈0．01）,其中麻黄提取物的作用明显大于另两种影响因素。麻黄提取物中醛质量分数达约1．6％。结论：麻黄软胶囊溶出迟缓与囊壳明胶发生交联反应有关,而麻黄提取物中醛类成分是促进软胶囊发生交联反应、导致其溶出迟缓的主要原因。     

对《中国药典》2010年版溶出度检查法的建议

溶出度检查是指片剂或胶囊剂等口服同体制剂在规定的介质中溶出的速度与程度.溶出的速度通过取样时间与溶出量控制,溶出量通过与标示量或本身的含量比较来控制.     

Box-Behnken设计-响应面法优化明胶胶皮处方

采用加热明胶、部分脱水山梨醇、甘油和水的混合物来制备明胶胶液,并加入遮光剂等其他成分制备明胶胶皮。以明胶种类、部分脱水山梨醇与甘油质量比、二氧化钛比例为自变量,以物质迁移率、平衡溶胀量、水蒸气透过率、透光率和崩解时间为因变量,采用Box-Behnken设计-响应面法优化胶皮处方,所得优化处方为：采用冻力150 g骨明胶,部分脱水山梨醇与甘油的质量比为2.3∶10,二氧化钛占明胶比例为1.18%。采用优化处方制备了3批胶皮,质量评价结果显示,其物质迁移率、平衡溶胀量、透光率的预测值与实测值偏差均≤1.7%,批间RSD均≤0.36%,表明所建立的优化处方准确性高、重现性好、稳定性良好。该研究为软胶囊工业化生产的改进提供了方法学参考。     

珍珠粉颗粒粒度与氨基酸体外溶出效果的关系

目的：测定不同粒度的珍珠粉氨基酸体外溶出量和溶出速率，考察氨基酸体外溶出效果。方法：选取不同粒度的珍珠粉体，以氨基酸为溶出指标，利用分光光度法测定其在一定时间内的溶出量和溶出速率，并对结果进行分析。结果：随着珍珠粉颗粒粒度的减少，氨基酸的溶出量增大，溶出速率加快，超细珍珠粉与未超细珍珠粉相比，表现得更加明显。结论：珍珠经超微细化后，可以大大提高珍珠粉氨基酸的溶出效果。     

复方鱼腥草配方合煎对黄芩苷和绿原酸成分溶出量的影响

目的:比较复方鱼腥草全方合煎与药材单煎对黄芩苷和绿原酸成分溶出量的影响.方法:采用高效液相色谱法,测定黄芩和金银花药材单煎提取物、全方合煎提取物中黄芩苷与绿原酸的含量.结果:全方合煎中的黄芩苷溶出量比黄芩单煎增加100%,相反,全方合煎中的绿原酸溶出量比金银花单煎降低25.4%.结论:复方配伍后煎煮对成分的溶出量有明显影响.     

银朱可溶性汞的含量测定

目的 建立测定银朱中可溶性汞的方法.方法 使用双硫腙分光光度法分析银朱在不同溶出介质、不同溶出转速、不同溶出时间下可溶性汞的含量.结果 选出溶出量最大的溶出介质为人工胃液,转速150 r·min-,时间2h,并建立相应的检测方法.结论 银朱汞的溶出量极少,具有安全性.     

HPLC法测定甘草锌胶囊的溶出度

目的:测定甘草锌胶囊中甘草酸的溶出量.方法:高效液相色谱法,用甘草酸单铵盐作为对照品,检测波长250nm.结果:溶出时间为45分钟,溶出量大于标示量的75%.结论:方法稳定,溶剂干扰小,专属性强.     

正交实验优选三伏贴中白芥子超微粉碎工艺

目的:优选三伏贴中白芥子超微粉碎工艺.方法:采用正交试验,以芥子碱硫氰酸盐百分之溶出量为评价指标,考察温度、超微加样量、超微前粒度、时间对粉碎工艺的影响.结果:影响芥子碱硫氰酸盐百分之溶出量因素次序为时间>加样量>超微前粒度>温度,最佳超微粉碎工艺为A3B1C3D2,即加样量1000g、粉碎前粒度80目、粉碎时间1.5h、粉碎温度0~15℃.结论:在此超微工艺下,芥子碱硫氰酸盐百分之溶出量最高,工艺可行.     

HPLC法测定盐酸左旋咪唑片的含量及溶出度

目的:建立HPLC法测定盐酸左旋咪唑片的含量及溶出度.方法:盐酸左旋咪唑含量用HPLC法测定,溶出度测定照<中国药典>2005年版二部附录溶出度测定法第一法进行.结果:盐酸左旋咪唑平均回收率99.2%,RSD为0.6%(n=6)溶出量大于标示量的90%.结论:方法简便适用于盐酸左旋咪唑片的质量控制.     

Swelling studies of gelatin. I: Gelatin without additives

The swelling rate and the equilibrium swelling of gelatin (type B) were studied by casting warm gelatin solutions into films, cutting them into short rectangular strips after gelation, drying them, and measuring the weight gain on immersion in buffer solutions as a function of time. The process variables investigated included concentration of the gelatin casting solutions, the thickness, drying conditions, age and residual moisture content of the film strips, the chemical nature and concentration of the buffers in the swelling solutions, and the temperature of these solutions at a constant pH of 7.0 (1.9 pH units above the isoionic point). The swelling kinetics followed a second-order equation. The initial swelling rate and the equilibrium swelling of the amorphous portion of the gelatin strips (which was somewhat smaller than the total observed swelling) were calculated from a linearized form of the rate equation. Of the factors investigated, the equilibrium swelling was increased most strongly when the temperature of the swelling solution was raised from 20 to 25 degrees C. Strip thickness was the predominant factor governing the rate of swelling, which was inversely proportional to the thickness. Conditions leading to slower drying and longer storage times promoted more extensive crystallization, thereby increasing the density of the gelatin strips and reducing their swelling rate.     

Swelling studies of gelatin. II: Effect of additives

Interactions between gelatin and six cationic, anionic, and nonionic drugs or excipients were investigated through their effects on initial swelling rate and equilibrium swelling of gelatin. Short rectangular strips of Type B gelatin containing the additives were immersed in buffer solutions of pH 7.0 at 20 degrees C. Their weight gain due to uptake of buffer solution and their weight loss due to leaching of the additive and of gelatin were determined as a function of time. During preparation of the strips, methyprylon and dicloxacillin sodium crystallized, while octoxynol 9 separated as small droplets in the gelatin matrix. Up to 7% of gelatin leached into the buffer solution during 96 h of immersion from strips of plain gelatin and strips containing five additives. The sixth additive, cetylpyridinium chloride, tripled the amount of gelatin leached while most of this additive remained in the gelatin strip. The other five additives were largely or completely extracted by the buffer solution. Potassium chloride underwent the fastest leaching, being completely dissolved within the first half hour. Octoxynol 9 was extracted most slowly because the swelling solution formed a viscous liquid crystalline phase inside the gelatin. Swelling followed second-order kinetics. Initial swelling rates and equilibrium swelling were calculated with a linearized function. Cetylpyridinium chloride, dodecylammonium chloride, and methyprylon reduced the initial swelling rate of gelatin while dicloxacillin sodium increased it. Octoxynol 9 and potassium chloride left it unchanged. Cetylpyridinium chloride and dodecylammonium chloride reduced the equilibrium swelling of gelatin substantially. Dicloxacillin sodium and octoxynol 9 increased it substantially, while potassium chloride and methyprylon increased it slightly. The extensive interaction of the cetylpyridinium ion with gelatin may result in reduced bioavailability.     

In vitro evaluation of the dissolution behaviour of itraconazole in bio-relevant media

Drugs in the gastrointestinal tract are exposed to a medium of partially digested food, comprising mixtures of fat, protein and carbohydrate. The dissolution behaviour of itraconazole was evaluated in bio-relevant media which were developed to take this into account. Media containing milk with different fat contents, protein (albumin, casein, gluten and gelatin), carbohydrates (glucose, lactose and starch) and amino acids (lysine, glycine, alanine and aspartic acid) to mimic a digested meal and bile components (sodium taurocholate and lecithin) to represent a key endogenous digestive material were investigated. The effect of medium composition on the intrinsic dissolution rate of itraconazole was evaluated as this drug has extremely poor solubility and its bioavailability is affected by food. Dissolution tests were carried out in simple compendial media based on dilute solutions of hydrochloric acid or neutral solutions of phosphate buffer and in more complex media containing the dietary components. The data obtained showed that most of the dietary components enhanced the solubility compared to simulated gastric fluid (SGF) but to differing extents. The greatest increase in dissolution was observed with the addition of milk and albumin although an increase was also seen with other proteins, amino acids and simulated gastrointestinal fluids.     

Dextran cross-linked gelatin microspheres as a drug delivery system.

This paper describes the use of oxidized dextran as a cross-linker for the preparation of gelatin microspheres. Microspheres were obtained by a thermal gelation method and their dissolution kinetic was examined. In order to find evidence of sugar mediated cross-linking, swelling tests and gelatin microspheres dissolution experiments were performed. The obtained results indicated that oxidized dextran can form a cross-linked gelatin network which can reduce the dissolution of gelatin. More interestingly, gelatin microspheres treated by both native and oxidized dextran slow down, even if to a different extent, the release of the antitumor drug TAPP-Br used as a model compound. Taken together, our results suggest that oxidized dextran could be an interesting means to cross-link gelatin microspheres allowing the use of this delivery formulation for controlled release of drugs.     

Examination of self-crosslinked gelatin as a hydrogel for controlled release.

A gelatin matrix crosslinked by extensive dehydration was examined for use in controlled drug delivery in this preliminary investigation. Crosslinking is necessary to prevent gelatin dissolution and immediate drug release at body temperature. Treatment at 105 degrees C and reduced pressure induced crosslinking in discs prepared from Type B gelatin. Crosslinking was evaluated by determining changes in gelatin solubility at 37 degrees C in a USP paddle dissolution apparatus. The crosslinking treatment was reproducible and resulted in 90% of the original gelatin mass remaining after 12 h in water and in phosphate buffer solutions of pH 3 and 6.4. The treated gelatin discs remained intact for greater than 24 h at pH 6.4. Chlorpromazine.HCl (CPZ) was incorporated as a model drug by soaking the treated gelatin discs in an aqueous solution of the drug. Release of CPZ at 37 degrees C in the dissolution apparatus was fitted to an empirical equation. A coefficient of this equation was used as the initial release rate for comparison between different release profiles. The roles of drug solubility, matrix swelling and erosion, and potential drug-matrix interactions were examined by conducting release studies at pH values of 3, 4, 6.4, and 7.4. The insoluble, un-ionized form of the drug had the slowest release rate. The soluble, ionized form under conditions of maximum swelling and a possible drug-matrix repulsive interaction had the fastest release rate. General electrostatic drug-matrix interactions were noted which could influence the drug release rate depending on conditions of the study. The times for 50% release of CPZ ranged from 1.8 to 11.3 h.     

Effect of Sodium Lauryl Sulfate in Dissolution Media on Dissolution of Hard Gelatin Capsule Shells

PURPOSE: Sodium lauryl sulfate (SLS) is a commonly used surfactant in dissolution media for poorly water soluble drugs. However, it has occasionally been observed that SLS negatively impacts the dissolution of drug products formulated in gelatin capsules. This study investigated the effect of SLS on the dissolution of hard gelatin capsule shells. METHODS: The USP paddle method was used with online UV monitoring at 214 nm (peptide bond). Empty size #0 capsule shells were held to the bottom of the dissolution vessel by magnetic three-prong sinkers. RESULTS: SLS significantly slowed down the dissolution of gelatin shells at pH < 5. Visually, the gelatin shells transformed into some less-soluble precipitate under these conditions. This precipitate was found to contain a higher sulfur content than the gelatin control sample by elemental analysis, indicating that SLS is part of the precipitate. Additionally, the slowdown of capsule shell dissolution was shown to be dependent on the SLS concentration and the ionic strength of the media. CONCLUSIONS: SLS interacts with gelatin to form a less-soluble precipitate at pH < 5. The use of SLS in dissolution media at acidic pH should be carefully evaluated for gelatin capsule products.     

Polyacrylamide microbeads,a sustained release drug delivery system

Using tetracycline-HCl and theophylline as model drugs, polyacrylamide microbeads were prepared by w/o emulsion polymerization technique. Furthermore, drug-loaded polymer microbeads were prepared in the presence of different concentrations of gelatin, which were further cross-linked for different time intervals. The prepared microbeads were characterized through particle size analysis, electron microscopy, and in vitro dissolution. Relatively spherical free-flowing populations of microbeads were obtained. The presence of gelatin during the polymerization processes led to larger particles proportional to its concentration in the aqueous phase. The dried microbeads showed smooth pored or fissured surfaces. In aqueous media, they attained equilibrium hydration within 10 min, with 73.5% v/v water uptake forming spongy spheres. The products showed slower dissolution rates with higher gelatin concentrations and extended cross-linking.     

Development of polysaccharide gel-coated pellets for oral administration. 2. Calcium alginate.

Calcium alginate gel-coated pellets were developed by forming an insoluble gel coat on extruded-spheronized pellets by interfacial complexation. Experiments were designed to investigate the effect of pellet size, alginate type, alginate concentration, and dissolution medium on swelling and drug release behavior. Low swelling in acidic media was related to proton-calcium ion exchange forming insoluble acid gels. In contrast, partial formation of soluble sodium alginate in 0.1M NaCl induced water uptake, resulting in greater swelling. Drug release from coated pellets showed a lag time when the gel coat hydrated and swelled, followed by a zero-order release. Significantly slower release was observed when either the pellet size or the alginate concentration was increased. Alginate with high guluronic acid content gave the slowest release. Different types of alginate with high mannuronic acid content showed different release behaviors that are probably due to the different monomer sequences and botanical sources. The faster drug release in acidic media and 0.1M NaCl compared to water is probably due to reduced calcium cross-linking in the gel. These results suggest that the pellet size, alginate type and concentration and dissolution medium influenced the swelling and drug release behavior of calcium alginate gel-coated pellets.     

Kinetics of swelling of polymers and their gels.

The swelling limit or equilibrium swelling of semicrystalline or cross-linked polymers and of their gels upon immersion in liquids has been investigated extensively. Few studies, however, have dealt with the kinetics of swelling. Theoretical considerations, based on diffusion-controlled swelling, show that first-order kinetics do not apply, even though deviations during the initial and even middle stages of the swelling process may be relatively small. Extensive studies of swelling rate and equilibrium swelling of supported and unsupported gelatin films have been published. Diffusion was always fast. After it was completed, the rate of swelling was controlled by stress relaxation in the amorphous portion of the polymer network. The rate equations for this process, which also apply to regenerated cellulose, are shown to represent second-order kinetics with respect to the remaining swelling capacity. The following interpretation for the applicability of second-order kinetics to the swelling of semicrystalline polymers, such as gelatin and cellulose, is given. The rate of swelling is assumed to be directly proportional to the percent swelling capacity still available at a given time and to the total internal specific boundary area enclosing those sites capable of swelling that have not yet become hydrated and swollen at that time. The latter, in turn, is also directly proportional to the percent unrealized swelling capacity.