Rheological Characterization of Topical Carbomer Gels Neutralized to Different pH

PURPOSE: The primary objective of this study is to perform detailed and extensive rheological characterization of rheology of carbomer (Carbopol) microgels formulated using a solvent system typically used in topical gel formulations. Solvents like glycerin and propylene glycol can alter rheology and drug delivery characteristics of topical gels owing to their different viscosities and due to the change in solvent-polymer and solvent-solvent interactions. METHODS: Aqueous gels with different pH were prepared by dissolving cross-linked Carbopol polymers in a co-solvent system comprising water, propylene glycol, and glycerol and subsequently neutralizing the carboxylic groups of the polymers with triethanolamine (TEA). Oscillatory, steady, and transient shear measurements were performed to measure viscoelastic properties, temperature dependency, yield strength, and thixotropy of carbomer pharmaceutical gels. RESULTS: The topical pharmaceutical gels exhibit remarkable temperature stability. Flow curves obtained at different temperatures indicate Carbopol microgels show much more pseudoplastic behavior (lower power law index) compared to Carbopol gels dissolved only in water. Substantial yield strength is required to break the microgel network of the topical gels. The gel samples exhibit modest thixotropy at higher deformation rates. CONCLUSIONS: The theological behavior of the Carbopol microgels do not change appreciably in the pH range 5.0-8.0, and the gels can be used as effective dermatological base for topical applications.     

Performance of an in vitro mucoadhesion testing method for vaginal semisolids: Influence of different testing conditions and instrumental parameters

The purpose of this work was to develop an in vitro mucoadhesion testing method for vaginal semisolid formulations. The proposed method was based on the measurement of the force (detachment force, Fdt) and the work (work of adhesion, Wad) needed to detach a sample of cow vaginal mucosa from a semisolid formulation, using a commercially available texture analyzer. Several testing conditions and instrumental parameters were tested in order to evaluate the mucoadhesive potential of a model vaginal semisolid formulation (1% Carbopol 974P gel). Also, mucoadhesive potential of several commercially available vaginal semisolid products was evaluated. Obtained results showed that the method is reproducible even when the same cow mucosa sample is used up to six times. The similarity of the fluid used to bathe the vaginal mucosa to the one naturally occurring in the vagina influenced considerably the performance of the test, advising that simulation of vaginal fluid properties is important when measuring mucoadhesive properties. Also, temperature of experiment was an important fact to be considered, as results showed slight but significant differences between body (37 degrees C) and room (20 degrees C) temperature. Fdt and Wad increased with increasing instrumental parameters while a plateau region was observable at higher values of probe speed, probe force, and mucosa/sample contact time. Comparison between results for Fdt and Wad demonstrated that although both parameters are generally in agreement, Wad seems to be more reliable and reproducible when evaluating mucoadhesion. Evaluation of commercially available formulations confirmed that experimental conditions are important features that can influence significantly the determination of mucoadhesive potential, being the proposed method an interesting and useful tool in the in vitro evaluation of vaginal semisolids.     

Contribution of high pressure to pharmaceutical and medical science

Since the beginning of the 20th century, effects of high pressure on biological systems have been studied, but the first applications in this domain have been developed in the 90's and concerned the preservation of food-stuff. Hence, much research work has been undertaken in order to develop high pressure effects in Biosciences. In the last decade, new methods or processes using high pressure (obtaining therapeutic molecules; decontamination or sterilization of biological stuff, sensitive drugs and drug carriers; development of vaccines; using high pressure as a tool in order to simulate and explore the mechanisms of proteins aggregation) underlining the potentialities of this technology in Medical and Pharmaceutical Sciences.     

Contribution of poly(amino acids) to advances in pharmaceutical biotechnology

Recently, protein biotechnology generates tremendous impacts in therapeutic products. These products include enzymes, antibodies, hormones, blood factors, growth factors and regulatory factors. Protein, vaccine and gene therapy drugs could be formulated with suitable biomaterials to deliver active agents to their target sites at the right time and maintain therapeutic effects for proper durations. In this review article, we focus on poly(amino acids) or polymerized amino acids for their applications in drug delivery systems, vaccines, and gene therapy. The nomenclatures of poly(amino acids) are briefly introduced to systematically express synthetic polypeptides. In drug delivery systems, we introduce two applications of poly(amino acids) in pharmaceutical biotechnology, either as carriers to facilitate drug delivery, or as biomaterials to be formulated as suitable delivery systems for application in tissue engineering. Many short polypeptides are mapped from antigen motifs and used for vaccination. These poly(amino acids) provide protective effects in animal challenge tests and potential application in vaccine development to be briefly introduced. Finally, some reports related to new developed poly(amino acids) as DNA carriers for achieving gene delivery are also described in the text.     

药物中有效成分含量测定能力验证项目研究

为评价全球各主要国家或经济体推荐的药品检测实验室的检测能力,经亚太实验室认可组织(APLAC)的授权,上海市食品药品检验所(SIFDC)和中国合格评定国家认可委员会(CNAS)共同组织实施了该能力验证计划(APLAC T080)。参加实验室采用高效液相色谱法测定复方卡托普利中氢氯噻嗪和卡托普利的含量。实施方采用了0.3σ法对能力验证样品进行了均匀性和稳定性实验,采用Z比分数法评定了各实验室的结果。以参加实验室测定结果的稳健均值作为氢氯噻嗪和卡托普利含量的指定值,以稳健标准差作为能力验证评估标准差。在18个国家或经济体推荐的38个实验室中33个实验室按时反馈了结果,其中24个实验室结果满意;5个实验室结果可疑;4个实验室结果不满意。     

Application of an improved procedure for testing the linearity of analytical methods to pharmaceutical analysis

Examination of the requirements of the Food and Drug Administration (FDA) for evaluating the linearity of an analytical method reveals them to be unsatisfactory, in both the definition of linearity and in the specifications for testing this property of an analytical method. A new definition for linearity is proposed, along with a new method for evaluating this property of an analytical method, one that is consistent with the definition. The method is tested by re-evaluating the linearity of data collected from a Near-Infrared method of analysis of pharmaceutical preparations.     

Contribution to the methodology of optimization and in-process control of some physical properties of pharmaceutical bulk substances and granulates

Many experts consider drug analysis exclusively as a chemical measuring technique. In the pharmaceutical industry, physical and physico-chemical parameters form an integrated part of the quality specification, because they play an essential role both in quality assurance and in the technical and economic aspects of production on the commercial scale. Such physical and physico-chemical properties are analysed by special, non-chemical methods. In their programme of systematic research in this field, the authors have elaborated new methods to test some essential properties of powders and granulates used in the production of compressed tablets. The following test and production methods have been developed: (i) the determination of flowing—sliding characteristics of granulates based on the measurement of the mass-flow (g s⁻¹) and mass-flow density (g s⁻¹ cm⁻²); (ii) the determination of optimum granulometric parameters with regard to tablet diameter; (iii) the direct determination of the temperature-dependent equilibrium vapour pressure; and (iv) the compression of tablets under controlled temperature.     

Challenge testing — The laboratory evaluation of the preservation of pharmaceutical preparations

The need for adequate preservation and the difficulties of definition and testing are outlined and pharmacopoeial challenge tests are compared. While similar in principle they differ in detail and in the interpretation of results. The USP test is intended for multi-dose sterile products but BP and draft EP tests include also criteria for topical and liquid oral preparations. Those of the BP, based on the performance of established well-preserved BP preparations, are not mandatory but provide guidance for the selection of suitable antimicrobial preservatives for inclusion in formulae of the Pharmacopoeia.