Tablet Disintegration Research Articles

Modification of natural hydrocolloid as disintegrant in aceclofenac tablet formulation

The purpose of present exploration was to modify kappa (k)-Carrageenan, by crosslinking, and assessed it as a tablet disintegrant to strengthen the solubility of the drug (aceclofenac) in tablet formulation. Modified k-Carrageenan was synthesized by reacting it with epichlorhydrin at heterogenous conditions. The swelling action of the product was investigated in order to optimize reaction circumstances for chemical cross-linking. Best modified k-Carrageenan procured by optimizing the reaction conditions and it was characterized for swelling index, particle size distribution, solubility, viscosity, gel strength and Fourier transform infrared spectroscopy (FTIR). Influence of modified k-Carrageenan on dissolution profile of therapeutic was also investigated along with other evaluation parameters. Modified k-Carrageenan exhibiting significant swelling index which is comparable to that of superdisintegrants. On comparative investigation as a tablet disintegrant by preparing anhydrous dicalcium phosphate tablet, modified k-Carrageenan showed disintegration time less than 20 seconds. Dissolution of aceclofenac (Class II) tablet formulaion utilizing modified k-Carrageenan was comparable with commercially available superdisintegrants. Faster dissolution of the accommodated drug was achieved with modified k-Carrageenan which was comparable with dissolution of the tablet formulation containing other superdisintegrants. The competent concentration of k-Carrageenan was found to be 5-15% as tablet disintegrant. Modified k-Carrageenan might be encouraging tablet disintegrant in fast dissolving formulations and can be worn in direct compression method. Keywords: k-Carageenan. Epichlorhydrin. Aceclofenac. Crosslinking. Superdisintegrant

L-T4 Therapy in Enteric Malabsorptive Disorders.

Levothyroxine (L-T4) absorption can be impaired by various causes: a) L-T4 ingestion during breakfast, or with food; b) conditions of reduced gastric acidity; c) intestinal procedures and diseases such as bariatric surgery, lactose intolerance (LI), celiac disease (CD), inflammatory bowel disease; d) drugs that alter L-T4 absorption, increasing the gastric pH, or preventing the dissolution of tablets. The development of new oral formulations, i.e. the liquid preparation and the soft gel capsule, represents the most recent advance regarding L-T4 therapy. Treating hypothyroidism with L-T4 tablets can lead to an improper control of thyroid-stimulating hormone (TSH) in ~10%–15% of patients. The improperly elevated TSH is usually managed by increasing the L-T4 daily dose, and revaluating TSH upon 2-6 months. The increase of the L-T4 dosage may cause iatrogenic hyperthyroidism, especially when the underlying disorders are cured. Liquid L-T4 can be administered in patients unable to swallow capsules or tablets, and this is one of its major benefits. Liquid L-T4 can: 1- overcome food and beverages interference; 2- bypass the malabsorption associated with an increased gastric pH; 3- circumvent the issue of malabsorption in patients who underwent bariatric surgery; 4-maintain TSH values under control better than L-T4 tablets in hypothyroid patients with typical or atypical CD, or in patients with LI. Few clinical studies evaluated soft gel L-T4 with encouraging findings in patients with gastric- or coffee-related malabsorption, or hypothyroid patients without malabsorption. Additional research is necessary to investigate liquid L-T4, or soft gel capsule, in other conditions of altered L-T4 absorption.

Tailoring crystal size distributions for product performance, compaction of paracetamol

Paracetamol crystals often exhibit poor compressibility properties, which results in capping issues. The Particle Size Distribution (PSD) of paracetamol was engineered to improve the compressibility of paracetamol crystals. This was accomplished by growing paracetamol crystals in the presence of additives. The active pharmaceutical ingredient Phenacetin and impurity 4-chloroacetanalide were used to modify the crystal properties of paracetamol. In solution, the phenacetin or 4-chloroacetanalide molecules adsorb onto the paracetamol crystal faces selectively (110 or 011) and inhibit the further growth of the paracetamol crystal and consequently, the paracetamol crystal growth is reduced substantially. For controlling the PSD of crystal to improve the compressibility of paracetamol crystals, a set of cooling crystallization experiments in the presence of additive was designed. According to a statistical experimental design, the cooling rate was the most effective parameter. The PSD was reduced when paracetamol crystallized from the controlled crystallization in the presence of less than 3 mol% of both additives. These smaller particles increased almost four-fold the compressibility of paracetamol in comparison to the commercial material. Moreover, tablets were prepared for each formulation using a direct compaction method. The results illustrated that a higher tablet hardness of paracetamol was achieved by tailoring the paracetamol crystal size distribution. In addition, the tablet disintegration time was higher for the formulation with increased hardness. Overall, this work presents the potential use of structurally similar compounds as additives to alter the mechanical properties of an API.

A REVIEW ON FAST DISSOLVING TABLETS

A REVIEW ON FAST DISSOLVING TABLETS Jyoti Saxena*, Digvijay Singh, Amrita Bisht, Arvind Negi, Aman Verma GRD Institution of Management & Technology (Pharmacy), Dehradun, Uttarakhand, India ABSTRACT As we are aware of the fact that Fast dissolving tablets have made an appearance as one of the most greatly welcomed dosage form, exceptionally between the pediatric patients and also among the geriatric patients, as both the category of patients have weaker muscular and the nervous system in comparison to adults as well as struggle to consume tablets and capsules. In the case of geriatric patients, Parkinson’s disorder and hand tremors are a major concern and Fast dissolving tablet is one of the most convenient dosage forms. The oral route is considered one of the best-preferred route to administer the drug in animal body but it also has few limitations too. For example, drugs have to go through first-pass metabolism, not preferred in psychiatric and bedridden patients. The FDTs are structured in a way to dissolve very quickly in saliva and this is the most celebrated property of FDTs, that these tablets disintegrate or dissolve in saliva in less than a minute and this process does not need water. Superdisintegrants like Crosscarmellose Sodium and Sodium Starch Glycolate are the backbones of the FDTs, which amplify the rate of disintegration of tablets inside the buccal cavity, results in faster absorption and finally improved bioavailability. There are a number of advantages are offered by FDTs which includes trouble-free transportation and manufacturing, error-free dose, remarkable physical and chemical stability, and above all, its acceptance among pediatrics and geriatric patients. FDTs provide the benefits of both the conventional tablets as well as of liquid dosage forms. FDTs can be manufactured by a number of conventional and patented technologies such as melt granulation, sublimation, direct compression freeze-drying or lyophilization, cotton candy process, etc. These techniques yield the rapid disintegration of tablets which dissolve in the buccal cavity in five seconds and do not need water and chewing. This review includes the definition, needs, advantages, and limitations, challenges to formulate and to manufacture the FDTs, and also some formulations of fast dissolving tablets which are available in market. Keywords: Fast Dissolving Tablet, drug delivery system, rapid disintegrating, fast melting Full Text Article

Evaluasi Pengaruh Konsentrasi Pati Biji Cempedak (Artocarpus champeden) sebagai Bahan Pengisi pada Formulasi Tablet Paracetamol

Cempedak plants are widely distributed in Indonesia, one of which is Kalimantan. Cempedak is a tropical plant, so its potential can be used as an additive in the manufacture of pharmaceutical preparations. Previous studies used cempedak seed starch as a binding agent in tablet formulations. This study aims to determine the effect of variations in concentration and optimum concentration of Cempedak seed starch (Artocarpus champeden) as a filler for Paracetamol tablets. The study used a True Experimental Design design with a posttest-only control group design. Making tablets using the wet granulation method. Data analysis used the one-way ANOVA test followed by the LSD test and the Kruskal-Wallis H test which continued with the Mann Whitney Test as a derivative test of the one-way ANOVA. Granule evaluation includes organoleptic, flow properties, tapping test, and stationary angle test. The results of the evaluation of the granules produced granules produced from each formulation are in accordance with the requirements. Tablet evaluation included organoleptic, uniformity in weight, the hardness of tablet, friability, and disintegration time. The results of the tablet evaluation showed that the maximum concentration of cempedak seeds was found in F1 because it showed the evaluation results that were in accordance with the requirements. In evaluating the uniformity of weight and hardness of tablets with the Kruskal Wallis H test and the Mann Whitney test, the results show that there are differences in each formula with a P-value <0.05. The results of the evaluation of tablet friability and disintegration time with one-way ANOVA test and LSD test showed differences in each formula with a P-value <0.05. Cempedak seed starch (Artocarpus champeden) can be used as a filler in the loading of Paracetamol tablets by the wet granulation method.

Pharmacomagnetography to evaluate the performance of magnetic enteric-coated tablets in the human gastrointestinal tract

A magnetic enteric-coated tablet containing diclofenac sodium was produced, and its performance under physiological and disturbed gastrointestinal motility was assessed through pharmacomagnetography analysis. In vitro studies were performed using conventional methods and in vivo studies were conducted on healthy volunteers before (control) and after domperidone administration. The magnetic tablet's gastrointestinal (GI) transit and disintegration process were monitored using the Alternating Current Biosusceptometry sensors combined with drug plasmatic concentration. The Gastric Residence Time, Colon Arrival Time, Small Bowel Transit Time, Disintegration Time and the pharmacokinetics parameters were calculated. The pH-dependent polymers used to coat the magnetic tablets were able to avoid the premature drug release on gastric or small intestine simulated medium. Gastric Residence Time was accelerated compared with the control group (p < 0.01). No significant differences were found regarding small bowel transit, colon arrival, disintegration process, or pharmacokinetics parameters. A strong correlation between magnetic monitoring and pharmacokinetics parameters analysis was determinant to evaluate the efficiency in the drug delivery at a specific site in the human gastrointestinal tract. In addition, a tablet with a damaged coating was used as a proof of concept to show the suitability of our methodology to evaluate the tablet. Our study showed that pharmacomagnetography is a multi-instrumental approach towards assessing drug delivery and bioavailability.

Evaluation of oral phytogenic microbeaded Newcastle Disease vaccine delivery in indigenous chicken

ABSTRACT This study describes the evaluation of microbeaded oral vaccine delivery for Newcastle Disease (ND) in village chicken. Microbeads containing vaccine were prepared by ionotropic-gelation technique using aluminum sulfate. Lasota Vaccine strain (2 g) was well mixed with Boswellia caterii gum extract at ratio 1:1. The wet beads were washed twice with distilled water and dried at 37℃ overnight. Microbeads without vaccine were prepared as control. A tablet dissolution machine was used to evaluate peak adhesion time (PAT). Sixty local chickens sourced from a recognized breeder were separated into four groups for in in-vivo evaluation. Group A was administered with the bead-loaded vaccine mixed with their feed, group B had vaccine alone administered in their drinking water, group C had the bead alone mixed with their feed, and group D, which served as negative control received no vaccination against ND nor gum beads. The PAT on both trachea and jejunum was 4 ± 10 hours. Post-vaccination antibody titer revealed higher response in group B than (6.6) in group A (5.3); the micro-beaded vaccine gave delayed but enhanced and prolonged immune response. This noninvasive and easy to administer method may be useful in the prevention of ND outbreaks in backyard poultry production.

Comparison of the effects on tablet disintegration of solvents used to dissolve food thickeners.

Food thickening agents help patients with dysphagia to eat, drink, and take medications. Taking medications with food thickeners has been reported to cause problems such as reduction of pharmacological effects through the delayed disintegration or non-disintegration of tablets. We previously reported that long immersion periods in food thickeners causes delayed disintegration and non-disintegration, while an immersion time of 1 min prevents these problems. However, in many studies including ours, water was used as the solvent, and patients with dysphagia use various drinks as food thickener solvents. Therefore, in this study, we examined the effects on tablet disintegration of food thickeners dissolved in 12 solvents. The line spread test (LST) and pH of the food thickeners differed among solvents, whereas the disintegration times of tablets immersed in food thickeners for 1 min were similar. Magnesium oxide tablets immersed in food thickeners for 30 min experienced delayed disintegration or non-disintegration in all solvents. These results suggested that the effects of solvents on the disintegration of medications hardly differ. Therefore, patients taking medications with food thickeners may refer to reports in which water was used as the solvent, regardless of their drink of choice.

Exploring the performance-controlling tablet disintegration mechanisms for direct compression formulations

The design and manufacture of tablets is a challenging process due to the complex interrelationships between raw material properties, the manufacturing settings and the tablet properties. An important factor in formulation and process design is the fact that raw material and tablet properties drive the disintegration and dissolution performance of the final drug product. This study aimed to identify the mechanisms which control tablet disintegration for 16 different immediate-release placebo formulations based on raw material and tablet properties. Each formulation consisted of two fillers (47% each), one disintegrant and a lubricant. Tablets were manufactured by direct compression using four different combinations of the fillers microcrystalline cellulose (MCC), mannitol, lactose and dibasic calcium phosphate anhydrous (DCPA). The disintegration mechanism was primarily driven by the filler combination, where MCC/lactose tablets were identified as wettability controlled, MCC/mannitol tablets as dissolution controlled and DCPA-based tablets (MCC/DCPA and lactose/DCPA) as swelling controlled. A change of 2% in porosity for the wettability controlled tablets (MCC/lactose) caused a significant acceleration of the disintegration process (77% reduction of disintegration time), whereas for swelling controlled tablets (MCC/DCPA) the same porosity change did not considerably impact the disintegration process (3% change in disintegration time). By classifying these formulations, critical formulation and manufacturing properties can be identified to allow tablet performance to be optimised.

Real-time release testing of dissolution based on surrogate models developed by machine learning algorithms using NIR spectra, compression force and particle size distribution as input data

In this work spectroscopic measurements, process data and Critical Material Attributes (CMAs) are used to predict the in vitro dissolution profile of sustained-release tablets with three machine learning methods, Artificial Neural Networks (ANN), Support Vector Machines (SVM) and Ensemble of Regression Trees (ERT). Beside the effect of matrix polymer content and compression force, the influence of active pharmaceutical ingredient (API) and matrix polymer particle size distribution (PSD) on the drug release rate of sustained tablets is studied. The matrix polymer PSD was found to be a significant factor, thus this factor was included in the dissolution prediction experiments. In order to evaluate the importance of the inclusion of PSD data, models without PSD data were also prepared and the results were compared. In the developed models, the API and hydroxypropyl-methylcellulose (HPMC) content is predicted from near-infrared (NIR) spectra, the compression force is measured by the tablet press and HPMC particle size is measured off-line. The predictions of ANN, SVM and ERT were compared to the measured dissolution profiles of the validation tablets, ANN yielded the most accurate results. In the presented work, data provided by Process Analytical Technology (PAT) sensors is combined with CMAs for the first time to realize the Real-Time Release Testing (RTRT) of tablet dissolution.

Clarification of the internal structure and factors of poor dissolution of substandard roxithromycin tablets by near-infrared chemical imaging

The spread of substandard and falsified medicines has become a global problem, especially in low- and middle-income countries (LMICs). Previously, we found that some tablets containing the same active ingredient had large differences in their dissolution even though their contents were comparable. In this study, we investigated the poor dissolution of roxithromycin tablets using near-infrared chemical imaging (NIR-CI) to visualize the internal tablet structure. Roxithromycin tablets collected in LMICs and the pioneer product Rulid® as a reference were cut to a flat surface for analysis. NIR spectral data were normalized, and a principal component analysis was performed to create a tablet internal structure image. For Rulid®, the differences between the spectra with high and low scores were small, and well-defined aggregation of ingredients was not observed. However, large differences in the scores were found for roxithromycin tablets manufactured in some LMICs, and non-uniformity of ingredient distribution and aggregation were observed. Additionally, some pharmaceutical excipients, such as starch or magnesium stearate, were found in certain aggregates by comparing NIR spectra. The NIR-CI results showed some excipients existed as large aggregates, which indicated that the ingredients were not evenly mixed in the roxithromycin tablet, and this contributed to its poor dissolution.

Disintegrant Properties of Microcrystalline Cellulose isolated from Rami (Boehmeria nivea L. Gaud) in Dimenhydrinate tablets by Wet Granulation and Direct compression

Microcrystalline cellulose was isolated from rami (Boehmeria Nivea L. Gaud), and applied as disintegrant in tablets of dimenhydrinate, made by direct compression and wet granulation. The aim of this study is to produce dimenhydrinate tablets with Microcrystalline Cellulose Rami (MCC Rami) isolated from Rami (Boehmeria Nivea L. Gaud), as a disintegrant and assess the effect of MCC Rami and Granulation technique on physical properties of drug such as, disintegration time, drug release and dissolution. Formulations of dimenhydrinate 100mg tablets were prepared with a combination of mannitol and lactose as a filler and MCC Rami as disintegrant in a concentration of 10-20%. The formulas were directly compressed or were compressed into tablets after wet granulation. The mechanical properties, drug release, physical properties and effects of process parameters, methods of applying disintegrant in tablet formulas were examined. A significant difference in disintegration time of tablets that were produced by direct compression and wet granulation was seen, that can be attributed to the porous structure of granules that enhanced fast disintegration, which had eventually improved dissolution and drug release. F1 and F2 with MCC Rami and physical mixture of MCC Rami with crosspovidone as a disintegrant that were directly compressed disintegrated in 79 and 72 seconds respectively thats not a significant difference, however when MCC was applied in an intragranular way its disintegration time is 67 seconds. The results showed that the method of disintegrant application and press of tableting has a significant effect on drug release and dissolution.Keywords : Microcrystalline Cellulose, wet granulation, disintegrant, Boehmeria Nivea L. Gaud.

Pregelatinized Starch: Variability in Gelatinization and its Influence on Product Performance

Starch and its derivatives are one of the significant excipients used in the pharmaceutical formulations due to their multi-purpose functionalities. The purpose of this study is two-fold: (1) Firstly, to propose a systematic approach in understanding the material properties of a starch derivative (pregelatinised starch/PGS) using analytical ‘toolbox’ as part of ‘alternative supplier sourcing’, and secondly (2) To demonstrate the effect of PGS from different vendors on the tablet disintegration using model formulations. Contextually, a two-tier characterisation procedure is generally considered as a prerequisite for establishing the sameness of the material obtained either from different batches or from various vendors. Primarily, the sameness between typical quality-control tests and compendial requirements are to be established. If similar, then sameness between the functional characteristics is to be established. In this context, the PGS from two vendors met the specifications, and there were no differences for the test results in the certificates of analysis. However, when subjected to functionality assessment, the two lots were found to be distinctly different. The influence of the functional property variations was further exemplified from viscosity results of raw material. Furthermore, this difference was even more evident when the model formulations were subjected to disintegration testing. The similarity in compendial tests but significant differences in functionality characteristics for the PGS of two vendors can be unravelled by considering variations in particle size, crystallinity, starch retrogradation and these changes are potentially attributed to the differences in the gelatinisation procedures adopted by the vendors.

A new perspective in understanding the dissolution behavior of nifedipine controlled release tablets by NIR spectroscopy with aquaphotomics

The in vitro dissolution profile is a key parameter which reflects the quality of sustained-release tablets. Most studies were used to determine the dissolution of tablets utilizing dissolution curves. This study aimed to investigate the role of water during nifedipine controlled release tablets dissolution process in order to provide a new way to understand the dissolution behavior. Dissolution liquid was added to the drug-containing layer slowly, and near infrared spectra were acquired according to the set time. NIR spectroscopy with aquaphotomics were introduced to determine different water patterns. The results showed that, the structural change of water was consistent with the dissolution process. During hydration stage, it was mainly Sr combined with the semi-permeable membrane to form a channel. Then S0, S1, S2 and S3 combined with the drug layer and the push layer. Finally, it was relied on the swelling of the push layer to push the drug layer out at the release process. This study not only deepens the understanding of the dissolution process, but also opens a new perspective in molecular interaction analysis in aqueous system by understanding the roles of water.

Compaction behaviour of mannitol-cocoa powder mixtures and their resulting tablet strength and disintegration characteristics

Cocoa powder is an important ingredient in the confectionery industry and, mannitol is an alternative sugar alcohol. In this work, mannitol powder was mixed with cocoa powder and compacted into tablet form via the uniaxial die compaction process. The frictional, compaction, tablet mechanical and disintegration properties were studied due to their importance in characterizing the behaviour of the tablets during processing and its final product characteristics at varying mannitol contents. The composition of mannitol in the mannitol-cocoa tablet varied at 95% w/w, 50% w/w and 5% w/w, while pure 100% w/w mannitol and cocoa tablets were set as controls. The compaction pressures used in making the tablets varied at 37.67 MPa, 75.34 MPa, 113.01 MPa, 150.68 MPa and 188.35 MPa. The compaction behaviour of the powder during the compaction process was evaluated using the plastic work and the maximum ejection stress values. The tablet strength was determined using the tensile strength method and tablet disintegration study was also conducted. The results showed that the increase in the compaction pressures increased the plastic work, maximum ejection pressure, tablet strength and also its disintegration time. The tablet formed having 95% w/w mannitol composition exhibited the highest plastic work value of 10.32±0.01 J, highest maximum ejection pressure value of 4.4±0.06 MPa, highest tensile strength value of 1.06±0.04 MPa and shortest disintegration time of 171±51 s amongst the three different mannitol compositions studied. Meanwhile, the effects of mannitol composition in the tablet on these observed responses were also dependent upon the compaction pressures used during tablet formation. In conclusion, the addition of mannitol improved the tablet strength and shorten the disintegration time in the experimental range employed in this study.

The elastic recovery, ejection work, strength and dissolution of instant coffee tablet containing croscarmellose sodium disintegrant

Croscarmellose sodium disintegrant agent, commonly used in the pharmaceutical tablet formulation was employed in the instant coffee tablet formulation. Various compositions of croscarmellose sodium were added to the instant coffee tablet formulation; 20% w/w, 40% w/w, 60% w/w and 80% w/w respectively. These mixtures were then compacted through the uniaxial die compaction process forming 1 g tablets having 13 mm diameters each at various compaction pressures of 37.7 MPa, 75.4 MPa, 113.0 MPa and 150.7 MPa. The ejection work done when ejecting the tablet from the die was calculated to represent the frictional resistance to tablet motion during ejection. The tablet elastic recovery was measured as a quantitative measure of the tablet physical dimensional stability. Meanwhile, the mechanical strength, as well as the tablet dissolution, were also measured. The results showed that the croscarmellose composition and the compaction pressure affected all the studied tabletting properties. Generally, croscarmellose sodium increased the tablet elastic recovery and lowered the tablet ejection work, tensile strength and dissolution time in experimental conditions employed in this work. However, the extent of the croscarmellose sodium influence was clearly dependent upon the compaction pressures used for instant coffee tablet formation.

In Vitro Evaluation of Native Taro Boloso‐I Starch as a Disintegrant in Tablet Formulations

Introduction. In drug delivery, solid dosage forms, of which tablet is the commonest, are still the leading preferences. An area of research focus in tablet drug delivery is the search for tablet excipients. This study was aimed at evaluating and optimizing native Taro Boloso‐I starch as a tablet disintegrant. Methods. The response surface method with central composite design (CCD‐RSM) was used for the analysis and optimization of the concentration of native Taro Boloso‐I starch and compression force. Wet granulation method was used for the preparation of paracetamol tablets. The response variables considered were tablet crushing strength, friability, and disintegration time. Results and Discussion. Both the native Taro Boloso‐I starch concentration and compression force had increasing effect on the tablet breaking force. The friability of the tablets was shown to decrease with increasing levels of the disintegrant concentration. On the other hand, compression force had a decreasing effect on friability in the investigated range. The disintegration time of the tablets was found to decrease with the concentration of the starch. The paracetamol tablets prepared with the optimized levels of native Taro Boloso‐I starch and compression force showed tablet breaking force of 116.24 N, friability of 0.153%, disintegration time of 1.36 min, disintegration efficiency ratio of 562.3 N/(%Min), and comparative disintegration efficiency ratio of 13.6 with respect to commercial potato starch. Conclusions. The tablets exhibited improved crushing strength, friability, in vitro disintegration time, and disintegration efficiency ratio which suggest the novel applicability of the native Taro Boloso‐I starch as an efficient pharmaceutical tablet disintegrant.

2E2-4 Ultrasonic tablet disintegration for controlled digestion

2E2-4 Ultrasonic tablet disintegration for controlled digestion

Liquisolid Tablets Formulation of Atorvastatin Calcium Using Polyethylene Glycol 400 as Solvent and Some Carrier Materials

The dissolution of atorvastatin calcium need to be improved since included BCS Class II drugs with low solubility and high permeability, meaning that the dissolution affects the bioavailability of drugs. This research aimed to develop a formulation of a liquisolid tablet using PEG 400 as a solvent and some carrier materials in various compositions to increase the dissolution of atorvastatin calcium. Different formulations of liquisolid tablets were conducted using different quantities of carrier and coating material for adsorbing liquid solvent to produce a free-flowing and compressible powder. Avicel PH 101, Avicel PH 102, Neusilin US2 were employed as the carrier and Aerosil 200 as the coating material. A disintegrant and lubricant were then added to the formed liquisolid system and compressed into tablets by the direct compressing method. The liquisolid tablets were characterized for their tableting properties and possible drug-excipient interaction by XRD and FTIR analysis. The tableting characteristics of atorvastatin calcium liquisolid tablets were within the acceptable limits criteria. The dissolution of AA4 and NA1 liquisolid tablets was higher compared to marketed tablets. Based on the XRD and FTIR analysis, no interactions between drug and excipient.

Assessment of the amorphous solid dispersion erosion behavior following a novel small-scale predictive approach

In general, the erosion rate of copovidone-based amorphous solid dispersions (ASDs) in contact with water diminishes with increasing drug load, causing poor drug release from the final drug product. A new easy-to-use tool with low material- and time-consumption, the microscopic erosion time test (METT), was established to allow prediction of the API-specific drug load threshold between an eroding and a non-eroding ASD. This API-specific drug load value is further described as the drug load dispersibility limit (DDL) and is the highest drug load at which an eroding ASD was still observed. A minor increase of 2.5% in drug load above the DDL already led to a non-eroding ASD and it was subsequently connected to the drug load-associated drop in API in vitro dissolution of ASD tablets and an impeded tablet disintegration. In total, 19 APIs in copovidone-based ASDs were characterized via the METT while a subset of these was investigated in more detail, namely indomethacin, celecoxib, dipyridamole, fenofibrate, naproxen and ritonavir. Furthermore, indomethacin- and celecoxib-containing ASDs with various drug loads were prepared and characterized to link the METT outcome with ASD tablet in vitro dissolution and disintegration performance.