Time-controlled release by the incorporation of superdisintegrants within the coat of zein dry coated tablets
Authors : Heba Abuzeineh, Safwan Abdel Rahim, Marco Cespi, Lorina Bisharat, Alberto Berardi
Abstract : The aim of this work was to develop zein-based press coated tablets for delayed, time-controlled drug release. Press coated tablets containing dextrates and chlorpheniramine maleate (BCS class 1 drug) in the core, and zein and either NaCl, sodium starch glycolate (SSG) or crospovidone (XPVP) in the coat were produced. Results show that tablets containing zein and NaCl in the coating could not release nearly any drug over 8 h. On the contrary, when SSG and XPVP were incorporated at a level of 8 % in the coating, a delayed drug release pattern was obtained, characterised by a lag-time of 3 h, followed by a burst of >80 % drug release over 6–7 h. Drug release was dependent on the concentration of SSG and XPVP in the formulations. Images of the tablets showed that during the lag-time the dosage forms did not change shape, although they started to swell. After this time, tablets gradually deformed and eventually ruptured. The lag-time is due to the time needed for the water to diffuse in, for the drug to dissolve and for the coating to become sufficiently permeable. The addition of the hydrophilic and swellable superdisintegrants SSG and XPVP to zein shifted the hydrophilic/hydrophobic balance of the coatings to higher hydrophilicity, thus enabling rapid hydration and drug release after the lag-time. This study demonstrates that zein-based macroscopic drug delivery systems can be tuned to tailor drug release to specific needs, i.e. delayed release in this case.
Keywords : Zein; Press coating; Lag-time; Swelling; Delayed release; Time-controlled release
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Advancing the understanding of the tablet disintegration phenomenon–an update on recent studies
Authors : Alberto Berardi, Lorina Bisharat, Julian Quodbach, Safwan Abdel Rahim, Diego R Perinelli, Marco Cespi
Abstract : Disintegration is the de-aggregation of particles within tablets upon exposure to aqueous fluids. Being an essential step in the bioavailability cascade, disintegration is a fundamental quality attribute of immediate release tablets. Although the disintegration phenomenon has been studied for over six decades, some gaps of knowledge and research questions still exist. Three reviews, published in 2015, 2016 and 2017, have discussed the literature relative to tablet disintegration and summarised the understanding of this topic. Yet, since then more studies have been published, adding to the established body of knowledge. This article guides a step forward towards the comprehension of disintegration by reviewing, concisely, the most recent scientific updates on this topic. Initially, we revisit the mechanisms of disintegration with relation to the three most used superdisintegrants, namely sodium starch glycolate, croscarmellose sodium and crospovidone. Then, the influence of formulation, storage, manufacturing and media conditions on disintegration is analysed. This is followed by an excursus on novel disintegrants. Finally, we highlight unanswered research questions and envision future research venues in the field.
Keywords : Disintegration; Disintegrants; Swelling; Wicking; Shape-recovery; Dissolution; Strain-recovery
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A facile and sensitive video-analysis method for tracking floating lag-time and floating rate of gastro-retentive tablets
Authors : Safwan Abdel Rahim, Marco Cespi, Lorina Bisharat, Alberto Berardi
Abstract : Floating effervescent tablets are designed to rapidly float in the gastric fluids by gas formation, after an initial lag-time. We developed here a method to characterise these dosage forms. Tablets were prepared containing various concentrations of hydroxypropyl methylcellulose (HPMC), dicalcium phosphate (DCP) and sodium bicarbonate (NB) as gelling agent, high-density model compound and gassing agent, respectively. Videos of the motion of tablets exposed to fluids for 6 h were recorded and then analysed to measure: i) tablet swelling; ii) floating kinetic until lag-time and iii) residual floating rate of the tablets over time. The developed technique was able to precisely track tablet motion and thus describe the floating performance of the dosage forms. Specifically, it was found that floating lag-time and floating fluctuations were influenced by the concentration of NB, more than DCP. Moreover, both swelling volume and residual floating rate over time were not affected by tablet composition, suggesting that density developments of the tablets were similar across formulations. Floating rate also remained constant over the test duration, which correlates well with previous findings on the floating force of HPMC/NB matrices. Overall, we showcase here a simple video-recording and -analysis technique to effectively characterise the performance of floating dosage forms.
Keywords : Floating lag-time; Floating tablets; HPMC; Gastro-retentive dosage forms; Image analysis; Floating rate
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Swelling of Zein Matrix Tablets Benchmarked against HPMC and Ethylcellulose: Challenging the Matrix Performance by the Addition of Co-Excipients
Authors : Alberto Berardi, Safwan Abdel Rahim, Lorina Bisharat, Marco Cespi
Abstract : Zein is an insoluble, yet swellable, biopolymer that has been extensively studied for its applications in drug delivery. Here, we screened the effect of co-excipients on the swelling and drug release of zein tablets. All throughout the study the behavior of zein was benchmarked against that of hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC). Tablets containing either zein, HPMC, or EC alone or in combination with co-excipients, namely lactose, dicalcium phosphate (DCP), microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), or sodium lauryl sulfate (SLS) were prepared by direct compression. Matrix swelling was studied by taking continuous pictures of the tablets over 20 h, using a USB microscope connected to a PC. The overall size change and the axial and radial expansion of the tablets were automatically extrapolated from the pictures by image analysis. Moreover, drug release from tablets containing ternary mixtures of zein, co-excipients and 10% propranolol HCl was also studied. Results showed that zein matrices swelled rapidly at first, but then a plateau was reached, resulting in an initial rapid drug burst followed by slow drug release. HPMC tablets swelled to a greater extent and more gradually, providing a more constant drug release rate. EC did not practically swell, giving a nearly constant drug release pattern. Among the additives studied, only MCC increased the swelling of zein up to nearly three-fold, and thus suppressed drug burst from zein matrices and provided a nearly constant drug release over the test duration. Overall, the incorporation of co-excipients influenced the swelling behavior of zein to a greater extent compared to that of HPMC and EC, indicating that the molecular interactions of zein and additives are clearly more complex and distinct.
Keywords : zein; swelling; matrix tablets; USB microscope; HPMC; ethylcellulose; excipients; image analysis
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Influence of calcium carbonate and sodium carbonate gassing agents on pentoxifylline floating tablets properties
Authors : Safwan Abdel Rahim, Paul Carter, Amal Ali Elkordy
Abstract : Purpose This study was to design and evaluate effervescent floating tablets with sustained release behaviour. Pentoxifylline is a water-soluble model drug with a short half-life, consequently developing sustained release preparations would be beneficial. Methods A binary (1:1) mixture of sodium alginate and hydroxyethyl cellulose containing pentoxifylline, with either 10% or 20% calcium carbonate or sodium carbonate, was used to prepare floating tablets. Results Tablets floated on the surface of the dissolution medium, showed an adequate floating lag time, and floated for more than 12 hours. Tablets manufactured from granules with 20%(w/w) calcium carbonate were promising with respect to their floating lag time (~ 7min), floating duration (> 24 hours), sustained drug release rate, and swelling ability. An in vivo study of these promising tablets and a reference solution of pentoxifylline were investigated following oral administration of 5.75 ± 0.15mg in rats. Compared with the reference solution, the pharmacokinetic parameters changed significantly (p < 0.05); the Cmax of the tablets was decreased (945.32ng/ml versus 2552.30ng/ml for the solution), while the Tmax and t1/2 were prolonged. Conclusion The study shows that a binary mixture of hydroxyethyl cellulose and sodium alginate, together with 20%(w/w) calcium carbonate, offers an exciting opportunity to develop sustained release pentoxifylline preparations.
Keywords : Pentoxifylline; Floating tablets; Hydroxyethyl cellulose; Sodium alginate; Calcium carbonate
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Optimization of pH-independent chronotherapeutic release of verapamil HCl from three-layer matrix tablets
Authors : Nizar Al-Zoubi, Hatim S Alkhatib, Ghadah Alobaidi, Safwan Abdel-Rahim, Wasfy Obeidat, Stavros Malamataris
Abstract : The aim of this work was to evaluate and optimize formulation of three-layer matrix tablets based on xanthan gum (XG) and sodium alginate for chronotherapeutic pH-independent release of verapamil HCl (VH). Artificial neural networks (ANN) were applied in the optimization and compared with multiple linear regression (MLR). A face-centered central composite experimental design was employed with three factors (mass fraction of VH in intermediate layer, X1, and of XG in matrix former of intermediate and outer layers, X2 and X3). The prepared tablets were tested for in vitro release in 0.1 N HCl and phosphate buffer (pH 7.5), tensile strength and friability. Furthermore, swelling observation and release modeling to Weibull function and power law equation of Peppas were employed to help further understanding of release behavior and mechanism. The releases (%) in phosphate buffer (pH 7.5) at 6, 12 and 24 h were selected as responses to depict the mode of release and similarity factor (f2), between release profiles in 0.1 N HCl and pH 7.5 during the first 8 h, as response of pH-independence. A desirability function combining the four responses was constructed and overall desirability values were used for the ANN and MLR modeling. Five additional checkpoint formulations, within the experimental domain, were used to validate the external predictability of the models. The constructed ANN model fitted better to the overall desirability than the MLR model (R = 0.838 vs. 0.670, for the additional checkpoint formulations) and therefore, was used for prediction of formulation with optimal in vitro drug release.
Keywords : Three-layer matrix tablets; Chronodelivery; Artificial neural networks; Xanthan gum; Sodium alginate
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Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug
Authors : Safwan Abdel Rahim, Paul A Carter, Amal Ali Elkordy
Abstract : 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, effervescent.
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Influence of ethanol on swelling and release behaviors of Carbopol®-based tablets
Authors : Safwan Abdel Rahim, Mutasim Al-Ghazawi, Nizar Al-Zoubi
Abstract : The aim of this work was to investigate the effect of ethanol on the in vitro swelling and release behaviors of Carbopol®-based tablets. The swelling behavior of drug-free compacts and the release of model drugs (metformin HCl, caffeine and theophylline) from matrix tablets were evaluated in acidic and buffered media with 0, 20 and 40% (v/v) ethanol. Release data were analyzed by fitting to Higuchi and Peppas models and calculation of similarity factor (f2). ANOVA tests were performed to determine significant factors on swelling and release. It was found that ethanol affects swelling and erosion of drug-free Carbopol® compacts, and the effect was highly dependent on medium pH. For matrix tablets, no dose dumping due to ethanol was manifested. The release rate and mechanism, however, were significantly affected by ethanol concentration as indicated by ANOVA applied to the constant, KH, from Higuchi model and the exponent, n, from Peppas model, respectively. The effect of ethanol on release was further confirmed by similarity factor results, which indicated that ethanol led to different release profiles (f2 < 50) in seven of eight cases for matrices containing metformin HCl and in three of eight cases for matrices containing caffeine and theophylline.
Keywords : Controlled-release; matrix; erosion; metformin HCl; caffeine; theophylline
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Tableting functionality evaluation of Prosolv Easytab in comparison to physical mixtures of its individual components
Authors : A Aljaberi, A Ardakani, A Khdair, SA Abdel-Rahim, E Meqdadi, M Ayyash, GM Alobaidi, N Al-Zoubi
Abstract : Prosolv Easytab is a recently introduced all-in-one excipient for direct compression. The aim of this work was to compare the compaction and dissolution functionalities of Prosolv Easytab versus équivalent physical mixtures of microcrystalline cellulose (MCC) or silicified microcrystalline cellulose (Prosolv SMCC) with complementary excipients. Lutrol F68 was used as a free flowing and poorly compactable model material for the comparison of the compaction functionality, and carbamazepine was used as a poorly soluble model drug for the investigation of the dissolution rate and dissolution stability after storage under accelerated stability conditions. Results showed that Prosolv Easytab produced comparable compactibility, dissolution and dissolution stability to its analogous physical mixtures based on MCC or Prosolv SMCC. The current findings suggest that Prosolv Easytab is functionally equivalent to physical mixture of its components, with obvious advantages regarding simplicity of manufacture and the potential masking of undesirable properties of individual components.
Keywords : Prosolv Easytab; Prosolv SMCC; Microcrystalline cellulose; Silicified microcrystalline cellulose; Coprocessed excipients; Compactibility
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