Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept

Context: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.

Objective: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.

Materials and methods: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.

Results and discussion: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed T_max, improved C_max and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.

Conclusion: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.     

溶胶-凝胶法制备HPMC／Si02杂化复合薄膜

采用溶胶-凝胶法（sol—gel）在聚乳酸（PLA）基膜上负载羟丙基甲基纤维素／二氧化硅（HPMC／SiO2）有机-无机杂化层,制备HPMC／Si02有杂化复合薄膜。表征和测试杂化复合薄膜的结构与性能。结果表明：当HPMC溶液体积分数为6％时,杂化复合薄膜的氧气阻隔性能比PLA薄膜的氧气阻隔性能提高了36倍,同时,杂化复合薄膜的拉伸强度优于PLA薄膜。     

The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets

Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.

Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.

Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL? K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.

Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.

Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.     

HPMC-based granules for prolonged release of phytostrengtheners in agriculture

One of the main aims in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high-quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular hydroxypropyl methylcellulose (HPMC) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.     

羟丙基甲基纤维素增韧水泥胶浆的配合比试验研究

羟丙基甲基纤维素溶液作为一种改性剂,掺入水泥胶浆中用于改善其韧性.采用正交试验研究了水胶比、纤维素溶液浓度和掺量对水泥胶浆的抗折强度、抗压强度及折压比的影响,并获得了最佳配合比.用单因素分析研究了减水剂和纤维素对强度和折压比的影响,以及纤维素对凝结时间的影响.最终结果表明羟丙基甲基纤维素可以改善水泥胶浆的韧性并对凝结时...     

添加HPMC对无麸质大米面包品质的影响

水稻是全球主导的粮食作物之一,作为无麸质食品的主要原料倍受青睐。但水稻中缺乏面筋蛋白,在发酵过程中难以形成持气性较好的网孔结构,所以很难获得理想的面包类发酵产品。本论文探讨了采用HPMC为面筋替代物制作无麸质大米面包的可行性,并研究了HPMC对大米面包品质的影响,从而为无麸质大米面包的制作奠定基础,为大米资源的广泛应用开辟新的途径。结果表明,当添水量提高到100%110%时,4%的HPMC可以作为面筋替代物,用以改善大米面团的品质,烘焙出优质、理想的无麸质大米面包,但其淀粉体外消化率和整体感官评价却受到影响。最后认为,应该把无麸质大米面包看作为一类新型的焙烤食品,不一定要完全适用小麦面包的评价体系。     

Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration

Objective: The effects of type and concentration of binding agent on properties of Eudragit RS based pellets were studied.

Materials and methods: Pellets containing ibuprofen (60%), Eudragit RS (30%), Avicel (10%) were prepared by extrusion spheronization. PVP K30, PVP K90, HPMC 6cp, HPMC K100LV or HPMC K4M were used as binders in concentrations of 2, 4 or 6% based on the total weight of formulation. The process efficiency, pellet shape, size distribution, crushing strength, elastic modulus and drug release were examined. The effect of curing on pellet properties was also investigated.

Results: The process of extrusion spheronization became difficult with increase in binder viscosity and/or concentration. An increase in binder viscosity and/or concentration resulted in reduction in the yield of pellets, wider particle size distribution and departure from spherical shape especially in the case of HPMC binder. The crushing strength and elastic modulus of pellets decreased with increase in PVPs concentration. However this was not the case for pellets containing HPMCs. Drug release rate increased as the concentration of binder increased. Pellets containing 2%w/w of PVP K30 showed the slowest release rate. For those pellets with brittle nature, curing changed the behavior of pellet under mechanical test to plastic deformation. Yield point and elastic modulus of all formulations decreased after curing. Curing decreased the drug release rate.

Conclusion: Binder type and concentration significantly affected the properties of pellets. For production of sustained release ibuprofen Eudragit RS based pellets lower viscosity binders (PVP K30) with concentrations less than 4%w/w was optimum.     

Droplet deformation and break-up under shear: Hydrocolloid solution vs. suspension of starch granules

Shear induced deformation and rupture of two types of droplets, hydroxypropyl methylcellulose (HPMC) aqueous solution and modified waxy maize suspension, were studied and compared using a counter-rotating rheo-optical set-up. The motivation of the work was to explain the difference observed in flavour perception of food products thickened by these two fluids. A droplet of either fluid was placed into silicon oil and deformation and break-up were monitored as a function of applied shear stress and strain. It was found that starch suspension droplets broke up at lower deformation stress and strain than HPMC solution droplets despite viscosity ratio and capillary number suggesting the opposite. It is hypothesised that the ease with which droplets thickened by starch break-up is responsible for their rapid mixing with saliva.     

羟丙基甲基纤维素分散剂对聚氯乙烯树脂颗粒特性的影响

研究了羟丙基甲基纤维素(HPMC)分散剂对悬浮PVC树脂颗粒特性的影响,分析讨论了HPMC与PVA的复合使用效果。结果表明,随着HPMC粘度的增加以及羟丙基含量的降低,分散能力减弱,保胶能力增强,PVC树脂的平均粒径和表观密度增大;HPMC与PVA复合使用,生产的PVC树脂具有颗粒形态好、粒径分布集中、孔隙率高等特点。     

Influence of surfactant properties on thermal behavior and sol–gel transitions in surfactant‐HPMC mixtures

Four surfactants, namely, sodium n‐decyl sulfate (SDeS), sodium n‐hexadecyl sulfate (SHS), sodium n‐dodecyl sulfate (SDS), and Triton X‐100, were used as additives to study thermal behavior and sol–gel transformations in dilute aqueous hydroxypropyl methyl cellulose (HPMC)/surfactant mixtures using micro‐differential scanning calorimetry. The influence of anionic surfactant, SDS on the gelation varied with SDS concentration where the sol–gel transition started at a higher temperature. Shape of the thermograms changed from single mode to dual mode at the SDS concentration of 6 mM and higher. SDeS and SHS, however, resulted in “salt‐in” effect of a different magnitude during gelation. Triton X‐100, being a non‐ionic surfactant, showed a minor “salt‐out” effect on the thermo‐gelation process. On the basis of different thermal behavior of anionic and non‐ionic surfactant/HPMC systems, a mechanism is proposed explaining how the chemical structure and electro‐charge of the surfactants affect the polymer/surfactant binding and polymer/polymer aggregation because of hydrophobic interaction during the sol–gel transition. © 2009 Wiley Periodicals, Inc. Journal of Applied Polymer Science, 2009