The gelling properties of Dillenia indica mucilage in benzyl benzoate emulgel formulations

Abstract The objective of the study was to evaluate the gelling properties of Dillenia indica mucilage in benzyl benzoate emulgel formulation. Mucilage was extracted from the fruits of Dillenia indica using established methods and characterized by rheology and swelling. Emulsion (F1) was prepared using the continental emulsification method. Gelling agents (2 %w /v) were prepared by dispersing in distilled water with constant stirring at a moderate speed using a magnetic stirrer. F1 was added to the gel (0-75 %w /w) to obtain emulgel formulations and evaluated using viscosity, globule size, pH, release profiles and kinetic modeling. Data were expressed as mean ± SD, and similarity factor (f2) was used to compare all formulations. Formulation viscosity was significantly higher with carbopol than with Dillenia; globule sizes increased with concentration of gelling agents, and pH reduced as the concentration of Dillenia increased. All formulations showed controlled release properties with t80 ranging between 114 and 660 min. The release was governed by Korsmeyer-Peppas model. Formulation F5 prepared with 50 % Dillenia showed highest similarity to F4 prepared with 75 %w /w carbopol. Dillenia indica demonstrated acceptable gelling properties comparable with that of carbopol and could be improved for use in emulgel formulations.

Application and research progress of in situ gel for local treatment of periodontitis / 中国药科大学学报

@#Recently, in situ gel has been widely used as a local delivery system for periodontitis treatment because of its lesion injectability, local drug depot function, and drug sustained-release effect.Different therapeutic purposes can be achieved by loading different types of drugs such as antibiotics, bioactive factors, etc.In this review, different types of in situ gel with temperature-sensitive, ion-sensitive, pH-sensitive and solvent-exchanged characteristics were introduced for their applications and limitations in the delivery of drug for periodontitis;and the elimination of periodontal inflammation, periodontal tissue repair and the long-term role after loading microsphere achieved by the in situ gel system were also reviewed.

Development and evaluation of liquid oral controlled release systems for Losartan potassium

Losartan potassium is a water soluble antihypertensive agent with short half-life. Controlling its release will improvepatient compliance. The benefit will be extended for geriatric patients if the developed system was liquid. The objectiveof this work was to develop controlled release oral liquid losartan potassium. This employed a combination of in situgelation and coating drug particles with pH-dependent polymer (Eudragit® L100). Solid dispersion (SD) prepared at1:1, 1:1.5, and 1:2 drug : polymer ratios, respectively. Sodium alginate solution was loaded with either pure drug orSD, in presence and absence of 1% w/v chitosan. These systems were evaluated for the drug release using continuouspH variation study. Alginate formulation with pure drug underwent in situ gelation in the gastric conditions but lost thegelling strength in the intestinal phase with burst drug release. Loading the formulation with SD resulted in controlleddrug release both in the gastric and intestinal phases. Increasing eudragit concentration in SD decreased the drugreleased with total release efficiency of 62.1%, 53.0%, and 41.7%. Incorporation of chitosan at reduced further drugrelease rate reaching 21% at the higher eudragit concentration. The study provided the formulator with a range of oralliquid formulations for controlled release of losartan potassium.

Development and in vitro/in vivo evaluation of thermo-sensitive in situ gelling systems for ocular allergy

Ocular allergy is one of the most common disorders of the eye surface. Following diagnosis this condition is typically treated with preparations containing antihistamines. However, anatomy of the eye and its natural protective mechanisms create challenges for ocular drug delivery. Rapid elimination of antihistamine substances due to short residency times following application can lead to insufficient treatment of ocular allergies. With this in mind, the aim of this study was to prepare a controlled ocular delivery system to extend the retention time of olopatadine hydrochloride (OLO) and in doing so to reduce the need for frequent application. We developed extended-release ocular in situ gelling systems for which in vivo retention times were determined in sheep following in vitro characterization and cytotoxicity studies. In vivo results were then compared to commercially available Patanol eye drops. the transparent gels formulated using appropriate amounts of polymers and having longer ocular retention times appear to be a viable alternative to commercially available eye drops.

Preparation process and in vitro evaluation of Shufei in situ gel optimized by central composite design-response surface methodology / 中草药

objective To optimize the preparation technology of sulfuric in situ gel and study the infiltration experiment of different dosage forms. Methods Shufei in situ gel was prepared by cold cut method with poloxamer 188 (P188) and poloxamer 407 (P407) as gel base. Using gelling temperature index, the dosage range of gel matrix P407 and P188 in Shufei in situ gel was determinated by the single factor and star design-response surface methods to get the best prescription of Shufei in situ gel. The transdermal diffusion process of Shufei in situ gel was carried out in Franz diffusion cells to explore the permeation mechanism. Results The optimized prescription of Shufei in situ gel was as follow: The ratio of gel matrix to drug at 1:3, P188 dosage of 4%, P407 dosage of 22.5%, and the phase transition temperature within 32-36 ℃ to form gel. The releases of sinapine thiocyanate and genkwanin in Shufei in situ gel were all in line with the Higuchi release model. Conclusion The preparation process of Shufei in situ gel is stable and feasible with reliable product quality and good application prospect, which is suitable for industrial production and clinical application.

New dosage forms for ocular administration / 中国药学杂志

Topical ocular medication is commonly used for eye diseases treatment.In view of low bioavailability and poor efficacy of traditional ocular preparations, the development of novel ocular drug delivery systems has become a great challenge in pharmaceutics.In recent years, nano preparations have been widely used for ocular drug delivery systems. At present, several nanocarriers, such as polymeric micelles, nanoparticles, nanosuspension, liposomes, emulsion, and dendritic polymers have been developed for ocular drug delivery.There are some other new dosage forms, such as in-situ gelling systems, implants, contact lenses, and microneedles are also under continuous research. The aim of development of these new dosage forms is to improve the drugs' ocular bioavailability and therapeutic effects.In this paper, the development in these areas in recent years are reviewed in order to provide reference for the development of new ocular drug delivery systems.

Medios de cultivo líquidos: un avance para la micropropagación comercial de zábila (Aloe barbadensis Mill.) / Liquid medium culture: an approach for the commercial micropropagation of aloe (Aloe barbadensis Mill.)

La micropropagación es una alternativa para la producción comercial de plantas de zábila (Aloe barbadensis Mill.) limitada por los altos costos de producción. Con el objetivo de prescindir de los agentes gelificantes, reduciendo costos, se comparó el medio de cultivo líquido con el medio de cultivo gelificado en las diferentes etapas de micropropagación de la zábila. En la etapa de establecimiento se observó mayor porcentaje de explantes contaminados en el medio de cultivo líquido estático (25.55 %) que en el medio gelificado (11.11 %); y aunque el resto de los explantes se establecieron independientemente de la condición del medio de cultivo, en el medio líquido alcanzaron mayor altura (3.81 cm) que en el medio gelificado (3.03 cm). En la etapa de multiplicación, la altura de los explantes (entre 4.43 y 6.01 cm) fue superior en los recipientes de inmersión temporal automatizado (RITA®) en comparación con el medio gelificado (entre 3.24 y 3.42 cm); sin diferencias significativas entre el número de brotes/explante. Todos los brotes enraizaron a los 30 días independientemente del medio de cultivo empleado (líquido estático y gelificado), sin observar variaciones en la altura del brote y, número y longitud de las raíces. El empleo de los medios de cultivo líquidos y la implementación de los sistemas de inmersión temporal tipo RITA® permiten reducir los costos de producción al prescindir de los agentes gelificantes, lo que representa un avance para la micropropagación comercial de zábila.

Micropropagation is considered a successful alternative for aloe (Aloe barbadensis Mill.) plant production. However, it has limited use due to the high production cost. Liquid media were compared to agar-gelled medium during all micropropagation stages of aloe to reduce the cost for gelling agent used. In the establishment stage, there was a higher percentage of contaminated explants in static liquid medium (25.55%) than those cultured in agar-gelled medium (11.11%), although all the explants were established independently of the culture medium used, higher height (3.81 cm) was observed in liquid medium than those growing in agar-gelled medium (3.03 cm). In the multiplication stage, explant height was higher in the recipients used for automated temporary immersion system (RITA®) (4.43 - 6.01 cm) than those cultured in agar-gelled medium (3.24 - 3.42 cm), there was no significant difference for number of shoots/explant. All shoots had roots at 30 days independently of used culture media (static liquid or agar-gelled media). Shoot height, number and root length had similar values in both culture media. The implementation of liquid media and automated temporary Immersion system RITA® may allow to reduce production costs of gelling agent used, it represents an approach for the commercial micropropagation of aloe.

Evaluation on rheological properties of Dange ophthalmic in-situ gel and its common gel / 中草药

Objective: To determine the rheological properties of Dange ophthalmic in-situ gel and its common gel by using dynamic rheological experiments. Methods: Dange ophthalmic in-situ gel was prepared by adopting Poloxamer as thermosensitive material, and Dange gel was prepared by carbopol. Anton Paar MCR302 Rheometer was used to determine the rheological parameters of above two kinds of gel at different temperatures which speculated the phase transition time and gelling temperature of in-situ gel. Results: Dange ophthalmic in-situ gel was Newtonian liquid at low temperature, with its viscous modulus dominated. It was shear-thinning pseudoplastic fluid under the conditions of phase transition at room temperature, with its elastic modulus dominated. The phase transition temperature (Tg) was (24.4 ± 0.1)°C, and the gelling time was 9 s. Dange gel existed in network structure among a certain temperature range, it was stable and did not change with temperature. Conclusion: The test has established the rheological evaluation system of Dange ophthalmic in-situ gel or its common gel, accurately evaluated the rheological properties of the two gels by dynamic rheological parameters, and it can be used as the basis for the quality control of products.

Valoración de endotoxinas bacterianas en el inyectable ácido zoledrónico mediante la prueba de lisado del amebocito de Limulus / Assessment of bacterial endotoxins in Zoledronic acid injectable drug by using Limulus amebocyte lysate test

Objetivo: valorar las endotoxinas bacterianas por la técnica del lisado del amebocito de Limulus para el producto inyectable ácido zoledrónico, por el método de gelificación. Métodos: el ensayo se realizó mediante dos pruebas: 1) confirmación de la sensibilidad del lisado etiquetado, para lo cual se preparó una curva estándar con diluciones seriadas dobles de endotoxina por cuadruplicado; y 2) el ensayo del producto de inhibición, en el que se prepararon diluciones seriadas dobles de endotoxina con agua apirogénica y con las muestras de los lotes a ensayar sin sobrepasar la máxima dilución válida. Se determinó el punto final y se calculó la media geométrica. Se definió la dilución de trabajo, la cual se validó por cuadruplicado en tres lotes consecutivos. Resultados: la sensibilidad del lisado resultó 0,03125 UE/mL. La máxima dilución válida fue de 112 UE/mL y la dilución de trabajo 1/100. La cantidad de endotoxinas bacterianas presentes en tres lotes del producto inyectable no sobrepasó el límite establecido, por lo que cumplió con las especificaciones de calidad establecidas para el ensayo. Conclusión: la estandarización de las condiciones del método por gelificación, hace que este resulte eficaz, confiable, rápido y de fácil ejecución, por lo que puede emplearse como ensayo de rutina en el control de la calidad del inyectable analizado

Objective: To asses the presence of bacterial endotoxins in Zoledronic Acid injectable drug by using the Limulus amebocyte lysate test, particularly by the gelling procedure. Methods: The assay was performed in two tests: the first was the confirmation of labeled lysate sensitivity by preparing a standard curve with serial double dilutions of endotoxins four times, and the second was the inhibition product test in which serial double dilutions of endotoxins were prepared with apyrogenic water and with samples from the batches to be tested, without exceeding the maximum valid dilution. The end point was determined and the geometric mean was calculated. Working dilution was defined and then validated four times in three consecutive batches. Results: The lysate sensitivity was 0.03125 EU/mL). The maximum valid dilution and the working dilution were 112 EU/mL and 1/100 EU/mL) respectively. The amount of bacterial endotoxins present in three batches of the injectable drug did not exceed the set limit, so it complied with the quality specifications for this test. Conclusions: The standardization of the gelling method conditions makes it possible to state that this method is effective, reliable, quick and easy-to-perform, so it can be used as a regular test in the quality control of the analyzed parenteral drug

Preliminary Study and Application on Cold Water Gelling Agent for Bacterial Testing Slip / 微生物学通报

0.05) of HKG testing slip had no significant differ-ence in statistics compared with pour plate method.As the gelling agent,HKG shows good performance in bacterial testing slip,and can also improve the detection efficiency.

Preparation and Quality Control of in-situ Gelling of Hydrochloride Sparfloxacin Eye Drops / 中国药房

OBJECTIVE:To prepare in-situ gelling of hydrochloride sparfloxacin eye drops and establish its quality con-trol method.METHODS:The in-situ gelling of hydrochloride sparfloxacin eye drops were prepared with boric acid as buffer to regulate the pH and osmotic pressure and with sodium polymannuronate as peptizer.The content of hydrochloride sparflo-xacin was determined by ultraviolet spectrophotometry.The stability of the sustained-release eye drops was investigated as well.RESULTS:The sustained-release eye drops were colorless or yellowish limpid liquid with its test and identification results all in conformity with the related stipulation stated in Chinese Pharmacopeia(2005 edition).There was a good linear relationship within the concentration range of 3.0～8.0 ?g?mL-1 for hydrochloride sparfloxacin,and its average recovery was 99.82%(RSD=0.236%,n=6).There was no significant change for indexes in the accelerate test and sample test,yet the temperature and lighting did have slight impact on the viscosity,osmotic pressure and pH of the solution.CONCLUSION:The preparative method is simple and feasible and the quality of in-situ gelling of hydrochloride sparfloxacin eye drops is stable and controllable.

Determination of fluconazole in tears and aqueous humors after topically applied to rabbit eyes by gas-liquid chromatography / 中华实验眼科杂志

Objective　To develop a rapid，sensitive and reliable high-performance gas chromatography to evaluate the fluconazole (FCZ) bioavailability after topically applied FCZ in-situ gelling ophthalmic delivery system to the rabbit eyes.Methods　A megabore capillary column（30m long and inner diameter of 0.530 mm） with a 0.88-μm-thick bonded liquid phase was used.Detector was nitrogen-selective type.Tears adsorbed to the filter paper was directly by methanol with no evaporation stage prior to analysis.Aqueous humors was extracted by ethyl acetate.Results　The duration of each analysis was less 10 min and the minimum detectable concentration was 0.01μg/ml.The assay was linear from 0.1 to 20 μg/ml.The average recoveries from tears and aqueous humors were 99.0% and 94.8%，respectively.Conclusion　This method can be used to determine rabbit tears and aqueous humors levels of fluconazole and was practicable approach for evaluating intraocular pharmacokinetics after topically applied to rabbit eyes.

Rheological properties and gel properties of agar / 中国海洋药物

Objective Rheological properties and gelation properties of agar were investigated. Methods The gelling point,melting point and the gel strength of agar were detected with MCR101 rheometer and TA texture testing instrument. Results and Conclusion Rheological properties of agar were affected by its concentration ,temperature and the addition of salt (such as NaCl ,CaCl2) and sucrose. Apparent viscosity exhibited shear thinning behavior following the power law model. Apparent viscosity increased with the increase of concentration,and decreased with the rise of temperature. The decrease in viscosity followed an Arrhenius temperature dependence. Agar solutions exhibited typical "weak gel" properties by small strain oscillatory measurements. The results indicated that the agar solution was characterized as a gel properties ,and which could form a kind of heat reversible gel. The gelling point of agar was lower than its melting point. The gel strength of agar could be affected by its gel time,and the addition of salt (such as NaCl,CaCl2) and sucrose.