Wet granulation to overcome liquisolid technique issues of poor flowability and compactibility: A study to enhance Glibenclamide dissolution

The aim of this study is to apply wet granulation on liquisolid powders to overcome issues of poor powder flowability and compressibility especially with using high viscosity liquid vehicles. Different liquisolid formulations were made using three excipients where the effect of each excipient used in the dissolution of the model hydrophobic drug (Glibenclamide) was evaluated. The Glibenclamide tablets were formulated using PEG 400, Synperonic PE/L44 and Cremophor ELP, at a 10 %w/w in liquid vehicle drug concentration. The carrier (Avicel®PH102) was used followed by colloidal silicon dioxide (coating material) that converted the wet mixture into dry powder. Potato starch, 5%w/w, as a disintegrant was mixed with the mixture manually for 10 minutes and was finalized by adding 0.75% of magnesium stearate as a lubricant. The final powder (depending on its flowability and compactability) was then compacted automatically using a single-punch tableting machine to give tablets with 4mg unit drug dose. Prepared liquisolid compacts were characterised via B.P. quality control tests. In this study, a novel discovery was achieved to overcome the major problems with liquisolid preparations (flowability and compactability). This new technique is the wet granulation process to be applied with liquisolid powders just before the compaction stage of the powders into tablets. Consequently, it was found that by application of wet granulation to liquisolid powder admixture, the large-scale production of liquisolid compacts is feasible and can be easily applied by pharmaceutical industry. As with some liquisolid vehicles especially high viscosity although very good to enhance dissolution usually formulations are studied in powder forms [1,2]

Insights into the influences of carboxymethyl-β-cyclodextrin on DNA formulations characteristics and gene transfection efficiency

BACKGROUND Gene therapy is an expanding field and it can treat genetic and acquired diseases. OBJECTIVE It was found that formulations with DNA: CM-β-CD (Carboxymethyl-beta-cyclodextrin): Pluronic-F127 1:3:3 and 1:3 DNA: CM-β-CD are the most stable formulations indicating high incorporation of DNA within CM-β -CD. METHOD Gel electrophoresis revealed DNA with low CM-β -CD concentration has formed a more stable complex. Samples 1:3 DNA: CM-β-CD and 1:3:3 DNA: CM-β-CD: Pluronic-127 show no DNA fragment, suggesting good condensation of DNA inside cyclodextrin cavity. RESULTS This was confirmed by fluorescence data where fluorescence intensity was reduced for samples DNA: CM-β-CD 1:3. Overall, the findings showed that Carboxymethyl-beta-cyclodextrin (as a novel non-viral gene vector) was able to provide condensation and protection to the DNA, with and without Pluronic-F127, at low concentration. CONCLUSION pDNA/CM-β-CD complex has not only shown to be able to transfect COS 7 and SHSY5Y cell lines, but it gives a higher transfection efficiency than that produced by the TransIT-LT1 commercial transfection reagent

Naproxen Microparticulate Systems Prepared Using In Situ Crystallisation and Freeze-Drying Techniques

Solaiman, A., Tatari, A.K. & Elkordy, A.A

Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug

The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer–Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50–54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile. Keywords: floating tablets, sodium alginate, pentoxifylline, dissolution, swelling, effervescen

An overview for the effects of lactitol, gelucire 44/14 and copovidone on lysozyme biological activity

Lysozyme, a model protein, was used to study the effects of excipients (lactitol, copovidone and gelucire 44/14) on the protein biological activity. Three different concentrations (0.1, 0.5 and 10 %w/v) of the excipients were used with a relatively high (10%w/v) lysozyme concentration. Analytical methods such as UV spectroscopy and fluorescence technique were used to study the effect of excipients on protein biological stability and integrity. The data obtained from analysis showed that gelucire 44/14 had a disadvantage effect on lysozyme stability as a single excipient. However, by combining gelucire 44/14 with lactitol, the protein activity was preserved. Also, the combination of lactitol and copovidone preserved the integrity and activity of 6% lysozyme to a great extent. Different excipients stabilised proteins to different degree. As conclusion, there is no excipient that works well for even one type of proteins. The most suitable excipient for each particular protein is found by extensive research studying the activity and stability of the protein in the presence of excipients. High efficacy and accuracy analytic methods should be used in order to give reliable information on protein stability and integrity. Keywords: lysozyme, lactitol, copovidone, gelucire 44/14, stability, biological activity

Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation

The production of biopharmaceutical formulation incorporates several difficulties embracing their physical and chemical instabilities. In this study, two drying techniques, namely, spray-drying and electrospraying, were used to assess their application on lysozyme (as a model protein) without and with the use of betacyclodextrin. Samples were prepared in the ratio of 1:1 w/w (protein/betacyclodextrin), and several characterisation methods were applied to study the percentage (%) yield, morphology of the produced partials, thermal stability and biological activity of the protein. The results show the two drying methods led to different particle morphology as spherical-like shape was produced by spray-drying, while rodlike shape was generated by electrospraying with larger particle size. Lysozyme formulations produced by electrospraying were stable just directly after preparation, but after few weeks, those formulations showed visible aggregates. The biological activity of lysozyme was preserved by both drying techniques. In conclusion, both drying methods have different effects on the protein integrity and biological activity in which spray-drying shows more promising results

Determination of folding reversibility of lysozyme crystals using microcalorimetry

Ye

Lysozyme and DNase I loaded poly (D, L lactide-co-caprolactone) nanocapsules as an oral delivery system

Abstract Clinical applications of oral protein therapy for the treatment of various chronic diseases are limited due to the harsh conditions encounter the proteins during their journey in the Gastrointestinal Tract. Although nanotechnology forms a platform for the development of oral protein formulations, obtaining physiochemically stable formulations able to deliver active proteins is still challenging because of harsh preparation conditions. This study proposes the use of poly (D, L-lactic-co-caprolactone)-based polymeric nanocapsules at different monomers’ ratios for protein loading and oral delivery. All formulations had a spherical shape and nano-scale size, and lysozyme encapsulation efficiency reached 80% and significantly affected by monomers’ ratio. Trehalose and physical state of lysozyme had a significant effect on its biological activity (P < 0.05). Less than 10% of the protein was released in simulated gastric fluid, and 73% was the highest recorded accumulative release percentage in simulated intestinal fluid (SIF) over 24 h. The higher caprolactone content, the higher encapsulation efficiency (EE) and the lower SIF release recorded. Therefore, the formulation factors were optimised and the obtained system was PEGylated wisely to attain EE 80%, 81% SIF release within 24 h, and 98% lysozyme biological activity. The optimum formulation was prepared to deliver DNase, and similar attributes were obtained