Influence of water-soluble polymers on the in vitro performance of floating mucoadhesive tablets containing metformin

Context: The in vitro performance of floating mucoadhesive metformin tablets was optimized using different polymer ratios of polyvinylpyrrolidone (PVP) tamarind seed gum (TSG) and hydroxypropylmethylcellulose (HPMC).

Objective: The objectives of this investigation were to investigate the combinatorial effects of PVP, TSG and HPMC; to study the work of adhesion measured on stainless steel (W_ss) and on rabbit gastric mucosa (W_gm); and a comparison of hydrophilic and more hydrophobic tablets.

Material and methods: In vitro performance was measured as tablet hardness (H), tablet floating lag time (FLT), time needed to release 60% of drug content (t_60%), swelling thickness (S), W_ss and W_gm. To compare the effects, a simplex lattice mixture design was used.

Results and discussion: H, FLT, W_ss and W_gm were found dependent on polymer ratio. H was increased when PVP ratio was increased. FLT, W_ss and W_gm were increased when HPMC ratio was increased. The p value for the lack of fit for all models were greater than 0.05. An approximate linear correlation between W_gm and W_ss was established (R²?=?0.71). The tablets containing PVP resulted in larger H, shorter FLT and t_60%, whereas W_ss and W_gm were enhanced.

Conclusion: The different in vitro performance of tablets containing different water-soluble polymers could be explained partially by the differences in the hydrophilic properties of the polymers and the ability of PVP to interact with HPMC or TSG. An equation established is used to conclude mucoadhesion based on adhesion measurements on stainless steel.     

The quality of evidence in tablet‐assisted interventions for students with disabilities

The purpose of this review is to weigh the evidence of the effectiveness of tablet‐assisted instructions (TAIs) at improving academic outcomes of students with disabilities. An extensive search process with inclusion and exclusion criteria yielded a total of 17 studies to be included in the present study: three group design studies and 14 single‐subject design studies. The quality indicators proposed by Gersten et al. ( 2005 ) and Horner et al. ( 2005 ) were applied to evaluate the methodological rigour of TAI studies and their feasibility to be considered evidence‐based. Results revealed that (a) most group design studies provided little information about the intervention agent and equivalence of groups across conditions, (b) the social validity of using tablets for students with disabilities was strongly established across all single‐subject design studies and (c) procedural fidelity in assessment and intervention implementation was inadequately addressed in group design studies. Although this review suggests that TAI used in single‐subject design studies can be a potentially evidence‐based practice for students with disabilities, there still remains to be established whether the group design studies can be considered evidence‐based, because of the lack of methodological rigour in group design studies. Finally, implications for future directions and practical ideas are discussed.     

HPLC法测定泛昔洛韦片有关物质

建立了高效液相色谱(HPLC)法测定泛昔洛韦片有关物质的方法。色谱柱为Agilent(C185μm,4.6mm×250mm),乙腈0.02mol/L磷酸二氢钾(20∶80)为流动相,流速为1.0mL/min,检测波长为221nm。该方法简便,准确,专属性强,可用于泛昔洛韦片中有关物质的测定。     

Evaluation of accelerated stability test conditions for medicated chewing gums

The overall stability of medicated chewing gums is investigated under different storage conditions. Active substances with different chemical stabilities in solid state are chosen as model drugs. The dosage form is a three layer tablet obtained by direct compression. The gum core contains the active ingredient while the external layers are formulated to prevent gum adhesion to the punches of the tableting machine. Two accelerated test conditions (40°C/75% RH and 30°C/65% RH) are performed for 6 months. Furthermore, a long-term stability test at room conditions is conducted to verify the predictability of the results obtained from the stress tests. Some drugs are stable in all the conditions tested, but other drugs, generally considered stable in solid dosage forms, have shown relevant stability problems particularly when stress test conditions are applied to this particular semi-solid dosage forms. For less stable drugs, the stress conditions of 40°C/75% RH are not always predictable of chewing gum stability at room temperature and may produce false negative; intermediate conditions, 30°C/65% RH, are more predictive for this purpose, the results of drug content found after 6 months at intermediate stress conditions and 12 months at room conditions are generally comparable. But the results obtained show that only long-term conditions stability tests gave consistent results. During aging, the semi solid nature of the gum base itself, may also influence the drug delivery rate during chewing and great attention should be given also to the dissolution stability.     

Development of a protocol to solidify native and artificial oil bodies for long‐term storage at room temperature

BACKGROUND: Oil bodies isolated from sesame seeds coalesced to form large oil drops when they were solidified in a drying process commonly used for food products. The aim of this study was to develop a protocol to solidify oil bodies for long‐term storage at room temperature. RESULTS: On the basis of testing several excipients, the coalescence of oil bodies could be effectively prevented when they were combined with mannitol. Sizes of oil bodies appeared similar under a light microscope before and after powderisation in combination with 70% or more mannitol. Artificial oil bodies were successfully generated with sesame oil, phospholipid and recombinant sesame caleosin. Following the developed protocol, native and artificial oil bodies were stably solidified in tablets. Both native and artificial oil bodies dissolved from the tablets remained stable after an accelerated stress test under a condition of 75% humidity at 40 °C for 4 months. CONCLUSION: A protocol was successfully developed for the solidification of native and artificial oil bodies in stable powder and tablet forms. This successful protocol is very likely to expedite the utilisation of artificial oil bodies in their potential applications. © 2012 Society of Chemical Industry     

Investigation of dissolution behavior of diclofenac sodium extended release formulations under standard and biorelevant test conditions

Background: Dissolution characteristics of four extended release (ER) generic formulations of diclofenac sodium were examined. Aim: The aim of this study was to compare the drug dissolution behavior of diclofenac ER generics to clarify whether the products are characterized by comparable dissolution characteristics under the applied test conditions. Methods: The investigations were performed in the USP apparatus 2 and in the new biorelevant dissolution stress test device. Results: The experiments yielded striking differences between the generic formulations. Applying USP apparatus 2 it was noticed that the dissolution profiles of the products were distinctly affected by the stirring rate. Using the biorelevant dissolution stress test device susceptibility of the products to biorelevant stresses was observed. Change of pH within the experiments reduced the dissolution rates of all formulations and distinctly influenced their dissolution characteristics. Conclusion: The study demonstrates clearly the divergences in the dissolution behavior among the generic ER formulations of diclofenac sodium. The observed susceptibility of the tested dosage forms toward biorelevant stress bears in our interpretation the risk to cause unwanted fluctuations in drug plasma concentration profiles.     

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.     

Influence of Tableting Forces and Lubricant Concentration on the Adhesion Strength in Complex Layer Tablets

The strength of adhesion in complex two-layer tablets is assessed using statistical methods with respect to the applied tableting forces for the first layer and for applying the second layer on the first, as well as regarding the fraction of the lubricant. These results, obtained on a single-punch tablet press, are compared with the results for three-layer tablets produced on a rotary press at production scale. The strongest negative influence on adhesion strength was exerted by the amount of lubricant in the central layer. As expected, compression forces for central-layer tableting also had a negative effect, whereas the compression forces for complex layer tableting exerted a positive effect on layer adhesion. The validity of the derived model equation was proved by experiments: It was shown that the adhesion strength in complex layer tablets produced in production scale can be predicted from laboratory-scale experiments. This makes optimization of the formulation and parameter settings at an early stage of development possible.     

Release of cyclobenzaprine hydrochloride from osmotically rupturable tablets

Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment. Tablets with increasing amount of PEO exhibited longer rupture times. This may be due to osmotic pressure-modulating properties of the polymer, changing the rate of water imbibition into the systems.

The integrity of the membranes was investigated using high-pressure mercury intrusion porosimetry. Minimal mercury intrusion into the membrane structure and core tablet indicated membrane integrity and lack of defective areas or pinholes. The results were in agreement with the release profiles where no drug release was detected prior to membrane rupture. Mercury intrusion porosimetry appears to be a promising technique for evaluation of membrane integrity.

Once the systems ruptured, drug was released by osmotic pumping and diffusion mechanisms through the ruptured area. There was a decrease in drug release rate with inclusion of PEO in the core.

The effects of film thickness on rupture and release times were also investigated. Devices with thicker films produced longer rupture times. This is in agreement with the theoretical prediction.     

粘质沙雷氏菌测量方法研究

粘质沙雷氏菌是生物防护评价的指示菌。对粘质沙雷氏菌营养琼脂平板涂布法进行了方法验证和协同实验验证以及不确定度分析。结果显示,该方法重复性和复现性均较好,室内重复性相对标准偏差为8.93%,室间相对标准偏差为14.95%。经统计分析,营养琼脂平板涂布法相对扩展不确定度为12.60%（k=2）,适用于粘质沙雷氏菌定量测量。