Excipients Mannitol Research Articles

Formulation of tablets containing lyophilized powder to improve the stability of alpha-chymotrypsin

This study aimed to develop a stable lyophilized formulation and the tableting process of lyophilized powder to improve the stability of the enzyme alpha-chymotrypsin (ACT). The impacts of the bulking agent and stabilizer on the freeze-drying process and the stability of ACT were determined. The effects of the filler excipients and the compression force on the activity of ACT tablets containing lyophilized powder were also evaluated. The findings revealed that arginine HCl, which had a multipoint interaction with the surface of ACT, and the crystalline excipient mannitol stabilized the structure of the enzyme and the lyophilized cake. The dehydration process through freeze-drying effectively protected the active substance against denaturing factors such as heat, moisture, and mechanical force. The study also demonstrated that the use of elastic fillers such as compressuc and a minor compression force contributed to the enhancement of ACT tablet stability. In summary, the study successfully developed a formulation for tablets containing ACT lyophilized powder, initially overcoming the poor stability of this enzyme to environmental factors, showing the applicability of lyophilization and stabilizing excipients in enhancing the stability of biomolecules.

Overview on Functionality Added Co-processed Excipients for Orodispersible Tablets

Orally disintegrating tablets are an emerging trend in novel drug delivery system and have received ever increasing demand during the last few decades. Orally disintegrating tablets ODTs are the dosage form which will disintegrate in mouth within seconds without need of water. This type of property in dosage form can be attained by addition of different varieties of excipients. But the number of fillers/binders/disintegrant which can be used for ODT formulations is limited because these bulk excipients have to fulfill special requirements, such as being soluble in water, pleasant taste, mouth feel, sweetness, and rapid dispersibility. In recent years drug formulation scientists have recognized that single component excipients do not always provide the requisite performance to allow certain active pharmaceutical ingredients to be formulated or manufactured adequately. New combinations of existing excipients are an interesting option for improving excipient functionality now a day. In excipients mannitol is used as diluents but now a day’s modified mannitol is available which give extensive flow, compression and rapid dispersibility to the tablet e.g. like Orocell, Mannogem EZ, and Pearlitol SD 200. The current review article is prepared to have a look over the recent development in excipient technology and the approaches involved in development of such excipients. It emphasizes on the different examples of functionality added materialsalso called as multifunctional co processed excipients available in market such as Ludiflash, Pharmburst, and F- MELT.

Contribution to determining the antioxidant capacity of melatonin in orodispersible tablets - comparison with reference antioxidants.

IntroductionMelatonin is a hormone used in the treatment of diverse pathologies due to its ability to regulate numerous physiological processes related to biological rhythms and neuroendocrine function.Material and methodsThis study examines whether or not the antioxidant capacities of melatonin are modified during the creation of fast disintegrating oral tablets (FDDTs) through direct compression in which different concentrations of the active substance (3, 5, 10 and 60 mg) and excipients are made. In addition, the antioxidant capacity of melatonin is compared with that of reference antioxidants such as vitamin C, Trolox, resveratrol, glutathione and nicotinamide adenine dinucleotide phosphate (NADPH).ResultsMelatonin has a lower antioxidant capacity only 5% of the capacity of resveratrol. Resveratrol is the compound having the greatest antioxidant capacity. As for the influence of the tablets components, it was found that only at higher concentrations of melatonin (60 mg/tablet), with the excipients mannitol, polyvinylpyrrolidone (crospovidone), magnesium stearate and anhydrous colloidal silica, did a decrease occur in the antioxidant capacity value, possibly due to the lower percentage of these excipients in the formulation.

Scaled-up production and application of co-processed excipient mannitol-HPMC in traditional Chinese medicine

Spray drying technology was used to produce co-processed excipients mannitol- hydroxypropyl methylcellulose (HPMC), and study the scaled-up production. The consistency of powder and tablet properties before and after scale-up of co-processed excipients was compared, and their applicability in traditional Chinese medicine (TCM) powder's direct compression was tested on five TCM extracts such as gardenia extract and Radix Paeoniae Alba extract. It was shown that after scaled-up production, the key properties of co-processed excipients had little changes (such as compactability, disintegrating time, and lubrication sensitivity) or improvement (such as flowability and yield). As compared to commercially available spray-dried mannitol, co-processed excipients achieved better compactability and higher drug loading for direction compression of TCM powder. In conclusion, the mannitol-HPMC co-processed excipient, with excellent physicomechanical properties, is promising to be explored as a new excipient for direct powder compression.

Preparation of naproxen–excipient formulations by CO2 precipitation on a slurry

The work focused on screening the impact of various excipients and/or procedure in a new method that consists in a CO2-induced precipitation of a drug on a slurry. Naproxen (NPX) is a drug whose bioavailability could be improved by formulation with hydrophilic excipients. The investigated excipients were of various type, size and porosity, i.e. mannitol, silicas (SiO2 and SIO2 aminopropyl) and an anion exchange resin Duolite. The precipitation process used compressed CO2 as antisolvent for NPX and acetone as solvent to dissolve NPX and to suspend the excipient particles. Naproxen precipitated as crystals with a size distribution influenced by the NPX:excipient ratio for mannitol-based formulations. For other excipient co-precipitates, the overall size distributions were in the same range and below 330μm except for the 5μm silica. Due to the hydrophilic nature of the excipients, most formulations yielded an increased drug dissolution rate. Compared to physical mixtures, the benefit of the CO2 treatment was demonstrated in case of the excipient mannitol.

Utilization study of filgrastim (Neutromax ®) during autologous haematopoietic precursor transplantation for myeloma and lymphoma patients

To describe utilization of a biosimilar product containing filgrastim (Neutromax ®), data of 414 myeloma or lymphoma patients subjected to autologous SCT between 1998 and 2007 were analyzed. Filgrastim was used for mobilization of progenitors (5 days at 300 μg/day) and for the recovery of neutropenia after transplantation (100 μg/day, since day +5). In 2003, the excipient mannitol was replaced by sorbitol. A mean dose of 9.47 × 10 6 CD34 + cells/kg was infused; 100 neutrophils/mm 3 required 5-day treatment; 500 neutrophils/mm 3, 6 days and 1000 neutrophils/mm 3, 7 days. Neutromax ® effect in SCT is similar to reports with other brands. No difference was found between formulations.

Classification of lyophilised mixtures using multivariate analysis of NIR spectra

Excipient selection is critically affecting the processing and the stability of a lyophilised product. Near infra-red (NIR) spectroscopy was applied to investigate freeze-dried samples containing varying ratios of the commonly used excipients mannitol and sucrose. Further variation in the formulation was achieved by adding NaCl, CaCl 2 and histidine and by exposing the samples to different conditions. Untreated NIR spectra are strongly affected by the physical nature of samples and can thus be useful for detecting production outliers. Applying standard normal variate (SNV) transformation highlights chemical information. The obtained NIR spectra of the freeze-dried samples were clustered by principal component analysis (PCA) after applying SNV correction in the range from 4200 to 7400 cm −1 (1350–2380 nm). Relative humidity under storage and the mannitol/sucrose ratio were clearly represented in the first two principal components, while influence of other excipients was observed in the 3rd and 4th principal component. It was investigated whether this could be due to an influence of the excipients on the mannitol crystallisation behavior. Performing PCA with two principal components of SNV-corrected spectra in the range 4200–4500 cm −1 (2220–1380 nm) led to the following observation: while the 1st principal component closely resembled the spectra of β-mannitol, the 2nd principal component contained additional features that were not attributable to β-mannitol but correlated well to the main absorbance band of δ-mannitol and mannitol hemihydrate. Therefore, it seems feasible that NIR can analyse versatile freeze-dried samples and classify these according to composition, water content and solid-state properties.

Vial lyophilization: calculations on rate limitation during primary drying.

The aim of this study was to assess the rate limiting factors in the sublimation phase of freeze drying and to propose a simple model on the basis of these rate limitations. A programmable freeze dryer was used. The load consisted of vials of varying size and various contents. To increase heat transfer, conductive paste was applied while the resistance toward mass transport was varied by using different restrictive capillaries. It was found that heat transfer limits the rate of sublimation. Presence of the commonly used excipient mannitol did not have a consequence on the rate of sublimation. The same applied for the restrictions towards mass transport. It was found that there exists not only a barrier against heat transport under the vial, but also between the glass wall and the frozen solution. From the results, a set of equations is proposed that enables to predict optimum sublimation conditions. For the pharmaceutical technologist this can serve as a simple and useful tool to derive a suitable freeze drying program.