Evaluation of the Effect of Disintegrant Distribution on the Dissolution Behavior of Pharmaceutical Tablets Using Raman Chemical Imaging.

In pharmaceutics, substandard drug manufacturing can sometimes occur. Usually, end-product release tests are conducted to detect defective products, but in many cases, they are not able to identify the root causes of quality defects. In recent years, chemical imaging techniques have been widely used to study quality defects by visualizing the distribution of components in solid dosage forms. However, in most studies, the causes are predicted from images of ingredients, and the impact of each factor is unclear. In this study, we prepared model tablets and intentionally changed only the distribution of disintegrants, and visualized this distribution using the Raman chemical imaging technique to evaluate the effect on the dissolution behavior of the tablets. We found that tablet disintegration occurs completely when the amount of disintegrant is sufficient to disintegrate the tablet and is distributed throughout the tablet, even if the distribution is not uniform. In contrast, if there was a large area where the disintegrant was not present, the tablet did not disintegrate sufficiently. This suggests that it is more important that a sufficient amount of disintegrant is present throughout the tablet rather than the degree of deviation of disintegrant distribution.

Quality Evaluation of Humidified Magnesium Oxide Tablet Formulations with Respect to Disintegration Time Prolongation.

In the present study, we conducted a detailed evaluation of the effects of humidification on the quality of five types of commercial magnesium oxide (MgO) tablet formulations. When near-IR spectroscopy was performed, a peak derived from the first overtone of the stretching vibration of the hydroxyl group was observed at approximately 7200 cm-1 in a humidified MgO tablet formulation. To visually evaluate the effect of this humidification, a mapping image was created using microscopic IR spectroscopy. In the IR spectrum, a peak derived from the stretching vibration of the hydroxyl group appears at approximately 3700 cm-1, so we created a mapping image using the absorbance ratio of 3700 and 3400 cm-1 as an index. In the mapping image of humidified MgO tablet formulations, many areas had a higher absorbance ratio than the dried tablet formulations. From these results, it is qualitatively confirmed that the MgO was changed to magnesium hydroxide (Mg(OH)2) by humidification. Although these results were observed in the four types of MgO tablet formulations, only one type of tablet formulation was less affected by humidification. In addition, although most tablet formulations tended to prolong disintegration time due to humidification, there was almost no effect of humidification on the disintegration time in one type of tablet formulation, which had little change in the above evaluation. Thus, in most commercial MgO tablet formulations, humidification prolongs the disintegration time, and Mg(OH)2 significantly contributes to this factor.

Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy.

The aim of this study was to evaluate the effect of three coformers and five disintegrants in the granulation formulation on the dissociation of cocrystal during the granulation process by monitoring wet granulation with probe-type low-frequency Raman (LF-Raman) spectroscopy. As model cocrystals, paracetamol (APAP)-oxalic acid (OXA), APAP-maleic acid (MLA), and APAP-trimethylglycine (TMG) were used. The monitoring of the granulation recipe containing cocrystals during wet granulation was performed over time with high-performance LF-Raman spectrometry and the dissociation rate was calculated from the results of multivariate analysis of LF-Raman spectra. The dissociation rate decreased in the order of APAP-TMG, APAP-OXA, and APAP-MLA, showing the same order as observed in Powder X-ray diffraction measurements. Furthermore, to compare the effect of disintegrants on the dissociation rate of APAP-OXA, LF-Raman monitoring was performed for the granulation recipes containing five typical disintegrants (two low-substitution hydroxypropyl cellulose (HPC), cornstarch (CSW), carmellose sodium (CMC), and crospovidone (CRP)). The dissociation rate of APAP-OXA decreased in the order of CSW, HPCs, CMC, and CRP. This difference in the dissociation rate of APAP-OXA was thought to be due to the disintegration mechanism of the disintegrants and the water absorption ratio, which was expected to affect the water behavior on the disintegrant surface during wet granulation. These results suggested that probe-type LF-Raman spectroscopy is useful to monitor the dissociation behavior of cocrystals during wet granulation and can compare the relative stability of cocrystal during wet granulation between different formulations.

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab.

BACKGROUND: Glioblastoma is one of the most aggressive and deadliest malignant tumors. Acquired resistance decreases the effectiveness of bevacizumab in glioblastoma treatment and thus increases the mortality rate in patients with glioblastoma. In this study, the potential targets of pentagamavunone-1 (PGV-1), a curcumin analog, were explored as a complementary treatment to bevacizumab in glioblastoma therapy. METHODS: Target prediction, data collection, and analysis were conducted using the similarity ensemble approach (SEA), SwissTargetPrediction, STRING DB, and Gene Expression Omnibus (GEO) datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using Webgestalt and DAVID, respectively. Hub genes were selected based on the highest degree scores using the CytoHubba. Analysis of genetic alterations and gene expression as well as Kaplan-Meier survival analysis of selected genes were conducted with cBioportal and GEPIA. Immune infiltration correlations between selected genes and immune cells were analyzed with database TIMER 2.0. RESULTS: We found 374 targets of PGV-1, 1139 differentially expressed genes (DEGs) from bevacizumab-resistant-glioblastoma cells. A Venn diagram analysis using these two sets of data resulted in 21 genes that were identified as potential targets of PGV-1 against bevacizumab resistance (PBR). PBR regulated the metabolism of xenobiotics by cytochrome P450. Seven potential therapeutic PBR, namely GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110 were found to have genetic alterations in 1.2%-30% of patients with glioblastoma. Analysis using the GEPIA database showed that the mRNA expression of ADAM10, AKR1B1, and HSD17B10 was significantly upregulated in glioblastoma patients. Kaplan-Meier survival analysis showed that only patients with low mRNA expression of AKR1B1 had significantly better overall survival than the patients in the high mRNA group. We also found a correlation between PBR and immune cells and thus revealed the potential of PGV-1 as an immunotherapeutic agent via targeting of PBR. CONCLUSION: This study highlighted seven PBR, namely, GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110. This study also emphasized the potential of PBR as a target for immunotherapy with PGV-1. Further validation of the results of this study is required for the development of PGV-1 as an adjunct to immunotherapy for glioblastoma to counteract bevacizumab resistance.

Effect of Disintegrants on Prolongation of Tablet Disintegration Induced by Immersion in Xanthan Gum-Containing Thickening Solution: Contribution of Disintegrant Interactions with Disintegration Fluids.

In clinical practice, a thickening solution is frequently used to allow easy swallowing of tablets by patients suffering from dysphagia. This study investigated the effect of the thickening solution on tablet disintegration. Model tablets containing different disintegrants were prepared and their disintegration times (DTs) measured using standard methods. We also performed an additional disintegration test on the model tablets after immersing them for 1 min in thickening solution containing xanthan gum (XTG-SOL) ("modified disintegration test"). The DTs of the test tablets were substantially prolonged by immersion in XTG-SOL. Furthermore, the effect of the XTG-SOL on the DTs differed depending on the type of disintegrant contained in the tablets. To investigate in more detail this prolongation of tablet disintegration, we examined the contribution of tablet properties to their DTs. The properties analyzed included contact angle, T2 relaxation time, wetting time, and water absorption ratio. The contributions of these properties to the DTs were analyzed using multiple regression analysis. This analysis clarified that the tablet properties affecting DTs changed after immersion in XTG-SOL: wetting time significantly affected the DTs measured in the normal disintegration test, while T2 was crucial for the DTs of tablets immersed in XTG-SOL. These findings provide valuable information for design of tablet formulations, and for clinical medication management for older patients with dysphagia.

Psyllium (Plantago Ovata Forsk) Husk Powder as a Natural Superdisintegrant for Orodispersible Formulations: A Study on Meloxicam Tablets.

(1) Background: In this work, we investigated the application of a natural superdisintegrant, psyllium (Plantago ovata Forsk) husk powder, for the manufacture of orodispersible meloxicam tablets. Meloxicam was chosen as a model compound for the study. (2) Methods: The tablets were prepared using different concentrations of psyllium husk by direct compression. Bulk density, tapped density, hardness, friability, in vitro disintegration, and dissolution time tests were used to assess the quality of the formulations. (3) Results: Psyllium husk powder significantly increased the dissolution rate of meloxicam. The formulation containing 16 mg of psyllium husk powder showed the lowest wetting time, the highest water absorption ratio, and the lowest disintegration time compared to the control and to the other formulations. These effects may be attributed to the rapid uptake of water due to the vigorous swelling ability of psyllium husk powder. (4) Conclusions: The powder could be recommended as an effective natural superdisintegrant for orodispersible formulations.

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

PURPOSE: To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. METHODS: A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. RESULTS: In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. CONCLUSION: In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

Functionality of wet-granulated disintegrant in comparison to directly incorporated disintegrant in a poorly water-soluble tablet matrix.

Tablet disintegration is crucial for drug release and subsequent systemic absorption. Although factors affecting the disintegrant's functionality have been extensively studied, the impact of wet granulation on the performance of disintegrants in a poorly water-soluble matrix has received much less attention. In this study, the disintegrants, crospovidone (XPVP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), were wet-granulated with dibasic calcium phosphate dihydrate as the poorly water-soluble matrix and polyvinylpyrrolidone as the binder. The effect of wet granulation was studied by evaluating tablet tensile strength and disintegratability. Comparison between tablets with granulated or ungranulated disintegrants as well those without disintegrants were also made. Different formulations showed different degrees of sensitivity to changes in tablet tensile strength and disintegratability post-wet granulation. Tablet tensile strength decreased for tablets with granulated disintegrant XPVP or CCS, but to a smaller extent for SSG. While tablets with granulated XPVP or CCS had increased disintegration time, the increment was lesser than for SSG, suggesting that wet granulation impacted a swelling disintegrant more. The findings showed that tablets with wet-granulated disintegrant had altered the disintegrant's functionality. These findings could provide better insights into changes in the disintegrant's functionality after wet granulation.

QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

BACKGROUND: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. RESULTS: Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

The Influence of the Intergranular Superdisintegrant Performance on New Drotaverine Orodispersible Tablet Formulations.

The main objective of this study consists in establishing the influence of the intergranular superdisintegrant on the specific properties of drotaverine hydrochloride fast-dissolving granules (DROT-FDGs) and orodispersible tablets (DROT-ODTs). The orodispersible tablets were obtained by the compression of the FDGs and excipient mixture with an eccentric tableting machine. To develop DROT-ODTs, two types of superdisintegrant excipients in different concentrations (water-soluble soy polysaccharides (SSP) (1%, 5%) and water-insoluble soy polysaccharides-Emcosoy® STS IP (EMCS) (1%, 3%, 5%)) were used, resulting in five formulations (D1-D5). The DROT-FDGs and the DROT-ODTs were subjected to pharmacotechnical and analytical evaluation. All the orodispersible tablets obtained respect the quality requirements in terms of friability (less than 1%), crushing strength (ranging between 52 N for D2 and 125.5 N for D3), and disintegration time (<180 s). The in vitro release of drotaverine from ODTs showed that all formulations presented amounts of active substance released greater than 85% at 10 min. The main objective, developing 30 mg DROT-ODTs for children aged between 6 and 12 years by incorporating the API in FDGs, was successfully achieved.

Evaluation of binders in twin-screw wet granulation - Optimal combination of binder and disintegrant.

The influence of localization (intragranular, split or extragranular) of three superdisintegrants (croscarmellose sodium, crospovidone, sodium starch glycolate) on granules and tablets after twin-screw granulation was studied. The aim was to find a suitable disintegrant type and disintegrant localization for lactose tablets manufactured with different hydroxypropyl cellulose (HPC) types. The disintegrants were found to decrease the particle size in granulation, where sodium starch glycolate had the lowest influence. The tablet tensile strength was not influenced strongly by the disintegrant type or localization. By contrast, the disintegration was dependent on the disintegrant type as well as the localization, where sodium starch glycolate performed worst. Intragranular croscarmellose sodium and extragranular crospovidone were identified as beneficial for chosen conditions because a satisfying tensile strength in combination with the fastest disintegration was found. These findings were achieved for one HPC type and the suitability of the best disintegrant-localization-combinations was confirmed for another two HPC types.

Non-destructive detection of disintegrant levels in compressed oral solid dosage forms.

Quality issues related to compressed oral solid dosage (OSD) forms, such as tablets, arise during the design, development, and production stages, despite established processes and robust production tools. One of the primary quality concerns is the disintegration properties and drug release profile of immediate-release OSD products, which depend on their micro-texture and micro-viscoelastic properties at the grain level. These properties are influenced by the composition of the formulation, particularly the disintegrant level in the tablet matrix and the porosity of the matrix. In this study, a novel, rapid, non-destructive ultrasonic characterization technique was proposed to correlate the sensitivity of propagating elastic wave speeds, physical/mechanical properties, and the dispersion profile of the OSD material with the disintegrant level (% w/w) in the formulation and the compression force applied during tableting. The proposed characterization framework involves transmitting pressure (longitudinal) and shear (transverse) waves through the OSDs to calculate the speed of sound, which in turn provides information on the apparent Young's and shear moduli. In addition, the attenuation profile of the propagating wave is obtained through dispersion analysis. To investigate the impact of disintegrants and compression force on ultrasonic wave propagation in OSDs, we incorporated seven levels of a frequently used disintegrant. In each formulation, OSDs are compacted in five compaction forces. The sensitivity of wave speeds, physical/mechanical properties, and attenuation profile was observed with each disintegrant and compression force level. The utilization of ultrasonic techniques may present a viable solution for rapid, non-destructive, non-invasive, and cost-effective testing methods required in continuous manufacturing (CM) and real-time release testing (RTRT), and its practical utility in pharmaceutical manufacturing is also discussed.

Effect of the mode of incorporation on the disintegrant properties of acid modified water and white yam starches.

Acid modified starches obtained from two species of yam tubers namely white yam - Dioscorea rotundata L. and water yam - D. alata L. DIAL2 have been investigated as intra- and extra-granular disintegrants in paracetamol tablet formulations. The native starches were modified by acid hydrolysis and employed as disintegrant at concentrations of 5 and 10% w/w and their disintegrant properties compared with those of corn starch BP. The tensile strength and drug release properties of the tablets, assessed using the disintegration and dissolution (t 50 and t 80 - time required for 50% and 80% of paracetamol to be released) times, were evaluated. The results showed that the tensile strength and the disintegration and dissolution times of the tablets decreased with increase in the concentration of the starch disintegrants. The acid modified yam starches showed better disintegrant efficiency than corn starch in the tablet formulations. Acid modification appeared to improve the disintegrant efficiency of the yam starches. Furthermore, tablets containing starches incorporated extragranularly showed faster disintegration but lower tensile strength than those containing starches incorporated intragranularly. This emphasizes the importance of the mode of incorporation of starch disintegrant.

Tableting Performance of Maize and Potato Starches Used in Combination as Binder/Disintegrant in Metronidazole Tablet Formulation.

Objectives: This study aimed to characterize the tableting performance of maize and potato starches, when used in combination either as a disintegrant or binder in solid dosage form development. Materials and Methods: Wet granulation was used to process metronidazole granules incorporating either maize starch, potato starch, or a combination of the two starches as binders or disintegrant at 10% w/w. Granule analysis was carried out on the various formulations and subsequently compressed into tablets weighing approximately 500 mg following the addition of extragranular excipients. Tablet properties were assessed after 24 h of storage. Results: Analysis of granule properties did not reveal a wide variation across the formulations irrespective of the type and combination of starches used in the formulation either as binder or disintegrant. It was observed, however, that there were slight differences in particle size, bulk and tapped densities of granule formulations containing the combined starch as excipients compared to granule formulations containing individual starch as the excipient. Tablets prepared using the combined starches as binder had lower tensile strength and disintegration time compared to other formulations incorporating the individual starches as binders. However, when evaluated as disintegrant, the tablet formulation containing the combined starches produced tablets with relatively lower disintegration time compared to formulations containing the individual starches as disintegrant. Conclusion: The study concludes that the combination of maize and potato starches as excipients in tablet formulation influenced the outcome of granule and tablet properties.

Time-domain NMR analysis for the determination of water content in pharmaceutical ingredients and wet granules.

The application of time-domain NMR (TD-NMR) analysis to quantify water content in pharmaceutical ingredients is demonstrated. The initial phase of the study employed a range of disintegrants with defined amounts of added water (0-30% of the total weight) as samples; the disintegrants included croscarmellose sodium, corn starch, low-substituted hydroxypropyl cellulose, and crospovidone. After acquisition of the T2 relaxation curves of the samples by TD-NMR measurements, these curves were analyzed by partial least squares (PLS) regression. According to the analysis, accurate and reliable PLS models were created that enabled accurate assessment of water content in the samples. A powder blend consisting of acetaminophen (paracetamol) and tablet excipients was also examined. Both a physical mixture of the powder blend and a wet granule prepared with a high-speed granulator were tested as samples in this study. Precise determination of water content in the powder blend was achieved by using the TD-NMR method. The accuracy of water content determination was equivalent to or better than that of the conventional loss on drying method. TD-NMR analysis samples were measured nondestructively and rapidly with low cost; thus, it could be a powerful quantitative method for determining water content in pharmaceuticals.

Evaluation of Microcrystalline Cellulose Derived from Saccharum officinarum L. (Sugarcane) Leaves as a Disintegrant in Tablet Formulations.

Purpose: Complete recycling of the crop residues of sugarcane in the Philippines remains to be achieved. This study purposed to derive microcrystalline cellulose (MCC) from sugarcane leaves and test its disintegrating properties in tablet formulation. Methods: Saccharum officinarum L. (sugarcane) leaves were used to prepare MCC powder. According to the conventional method, the preparation of cellulose powder requires heating the raw material with acid and alkali followed by washing, bleaching, and sieving. Hydrolysis of the bleached product was carried out using hydrochloric acid to obtain MCC powder, and the physicochemical properties of the produced MCC powder were studied including its organoleptic properties, pH value, %loss on drying, %water soluble substances and Fouriertransform infrared (FTIR) spectrum. Results: The resulting powder was evaluated for its disintegrating property in the preparation of blank tablets, which were compared to tablets prepared using commercially available MCC. MCC powder derived from sugarcane leaves had properties at par with commercially available MCC and was in conformance with National Formulary (NF) specifications. Conclusion: Disintegrating properties were also significantly better than the commercially available MCC.

Development of the Modified Ocimum gratissimum Seeds for Orally Disintegrating Tablets.

BACKGROUND: Natural materials have been encouraged in controlled drug release and improved drug bioavailability. OBJECTIVE: This study aimed to develop a modification process for the use of a natural material, Ocimum gratissimum seeds (OGS), in Orally Disintegrating Tablets (ODTs). METHODS: The OGS was investigated with four different modification processes including only milling, swelling, swelling/milling, and swelling/milling/incubation. The ODTs containing the modified OGS as a disintegrant were prepared by the wet granulation method. Furthermore, an evaluation to assess parameters of tablets, such as weight variation, hardness, friability, wetting time, disintegration time, drug content, and dissolution studies, was performed. RESULTS: The modification of OGS using the swelling/ milling process resulted in a completion of OGS modification, leading to an ideal wetting time, disintegrating time, and dissolution rate. The OGS concentrations also affected the wetting and disintegrating time with the optimal range of ODTs from 15% to 20%. On the other hand, the modification with the incubation processes varied by temperature and time increased the wetting time and disintegrating time. CONCLUSIONS: The modified OGS demonstrated that it is a potential material with the advantages of cost-effectiveness, non-toxicity and easy manufacture in the preparation of ODTs.

Effect of the molecular mobility of water adsorbed by disintegrants on storage-induced hydrolytic degradation of acetylsalicylic acid incorporated into tablets under humid conditions.

The purpose of this study was to investigate the effect of molecular mobility of water adsorbed by disintegrants on the hydrolytic degradation of active pharmaceutical ingredients (APIs). Fourteen different disintegrants were tested. First, powdered disintegrants were stored at conditions of 40 °C/75% relative humidity ("humid conditions") and their T2 relaxation times were measured by time-domain nuclear magnetic resonance for examination of the molecular mobility of water adsorbed by the disintegrant. From the observed T2 values, the water molecular mobility was fully characterized. In particular, the molecular mobility of water adsorbed by crospovidones was much higher than the molecular mobility of water adsorbed by the other test disintegrants because of longer T2 values. The next study examined the hydrolytic degradation of acetylsalicylic acid (ASA), a model moisture-sensitive API, stored under humid conditions. Physical mixtures of ASA and disintegrants or their model tablets were used as test samples, and they were stored for 7 d. The disintegrants contained in the samples clearly affected the ASA degradation: the most significant ASA degradation was observed for the crospovidone-containing samples. Finally, we analyzed the effect of the molecular mobility of water adsorbed by disintegrants on the ASA degradation by the least absolute shrinkage and selection operator (Lasso) regression techniques. As in the T2 experiment, various properties of disintegrants (i.e., water content, pH, and water activity) were used in this experiment as the explanatory variables. From the Lasso analysis, we successfully showed that the higher molecular mobility of water adsorbed by disintegrants significantly enhanced ASA degradation. These findings provide profound insights into the chemical stability of moisture-sensitive APIs in tablets.

Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets.

Metoclopramide hydrochloride (MCP) is commonly used for the management of gastrointestinal disorders. Frequent administration and the undesired side effects (extra pyramidal symptoms) of the drug on the central nervous system due to the fluctuations of its plasma concentrations may lead to patient incompliance, and hence, improper therapy. Therefore, the present work will be devoted to formulate the drug in sustained release formulations. MCP was incorporated in 12 formulae containing different polymers and/or different polymer ratios. These polymers were hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose (CMC) and ethyl cellulose (EC). Sodium starch glycolate (SSG) was added to some formulae in different amounts in order to soften and/or disintegrate the tablets. Both direct compression and granulation techniques were used to prepare the tablets. The physical properties were found to be satisfactory for all the formulae. The dissolution profiles of the tablets were constructed using the change-over method. The drug release involved a combination of both diffusion and polymer-chain relaxation mechanisms. The time required to release 50% of MCP ranged from 1.2 to more than 8 h. Direct compression and dry granulation techniques produced sufficient sustaining of the drug release. However, the pellets made by wet granulation released MCP in about 2 h, i.e., pelletization spheronization technique was not effective in sustaining the drug.