A prediction model based on artificial intelligence techniques for disintegration time and hardness of fast disintegrating tablets in pre-formulation tests.

BACKGROUND: The pharmaceutical industry is continually striving to innovate drug development and formulation processes. Orally disintegrating tablets (ODTs) have gained popularity due to their quick release and patient-friendly characteristics. The choice of excipients in tablet formulations plays a critical role in ensuring product quality, highlighting its importance in tablet creation. The traditional trial-and-error approach to this process is both expensive and time-intensive. To tackle these obstacles, we introduce a fresh approach leveraging machine learning and deep learning methods to automate and enhance pre-formulation drug design. METHODS: We collected a comprehensive dataset of 1983 formulations, including excipient names, quantities, active ingredient details, and various physicochemical attributes. Our study focused on predicting two critical control test parameters: tablet disintegration time and hardness. We compared a range of models like deep learning, artificial neural networks, support vector machines, decision trees, multiple linear regression, and random forests. RESULTS: A 12-layer deep neural network, as a form of deep learning, surpassed alternative techniques by achieving 73% accuracy for disintegration time and 99% for tablet hardness. This success underscores its efficacy in predicting complex pharmaceutical factors. Such an approach streamlines the drug formulation process, reducing iterations and material consumption. CONCLUSIONS: Our findings highlight the deep learning potential in pharmaceutical formulations, particularly for tablet hardness prediction. Future work should focus on enlarging the dataset to improve model effectiveness and extend its application in pharmaceutical product development and assessment.

Novel bioequivalent oral disintegrating tablet of aripiprazole prepared by direct compression technique with shortened disintegration time.

Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet). The ODT with 3.1-5.2 kp hardness exhibited rapid disintegration (14.1-17.2 sec), along with appropriate mechanical strength (friability < 0.24%). In a bioequivalent study in Korean healthy subjects (randomized, single-dose, two-period crossover design, n = 37), the novel ODT offered the equivalent pharmacokinetic profile to that of a conventional immediate release tablet (Otsuka, Abilify®, Japan), despite different disintegration and dissolution profiles. The 90% confidence intervals of the geometric mean test to reference ratios considering the area-under-the-curve and maximum plasma drug concentrations were 1.0306-11051 and 0.9448-1.1063, respectively, satisfying FDA regulatory criteria for bioequivalence. The novel ART ODT was physicochemically stable under the accelerated storage condition (40 °C, RH75%) for 24 weeks. Therefore, the novel ARP-loaded ODT is expected to be an alternative to oral ARP therapy, providing improved patient adherence.

Investigating the Impact of Co-processed Excipients on the Formulation of Bromhexine Hydrochloride Orally Disintegrating Tablets (ODTs).

PURPOSE: Orodispersible tablets (orally disintegrating tablets, ODTs) have been used in pharmacotherapy for over 20 years since they overcome the problems with swallowing solid dosage forms. The successful formula manufactured by direct compression shall ensure acceptable mechanical strength and short disintegration time. Our research aimed to develop ODTs containing bromhexine hydrochloride suitable for registration in accordance with EMA requirements. METHODS: We examined the performance of five multifunctional co-processed excipients, i.e., F-Melt® C, F-Melt® M, Ludiflash®, Pharmaburst® 500 and Prosolv® ODT G2 as well as self-prepared physical blend of directly compressible excipients. We tested powder flow, true density, compaction characteristics and tableting speed sensitivity. RESULTS: The manufacturability studies confirmed that all the co-processed excipients are very effective as the ODT formula constituents. We noticed superior properties of both F-Melt's®, expressed by good mechanical strength of tablets and short disintegration time. Ludiflash® showed excellent performance due to low works of plastic deformation, elastic recovery and ejection. However, the tablets released less than 30% of the drug. Also, the self-prepared blend of excipients was found sufficient for ODT application and successfully transferred to production scale. Outcome of the scale-up trial revealed that the tablets complied with compendial requirements for orodispersible tablets. CONCLUSIONS: We proved that the active ingredient cannot be absorbed in oral cavity and its dissolution profiles in media representing upper part of gastrointestinal tract are similar to marketed immediate release drug product. In our opinion, the developed formula is suitable for registration within the well-established use procedure without necessity of bioequivalence testing.

Evaluating the Effect of Microcrystalline Cellulose Variations on Tablet Quality of Natural Plant Product Using a Design of Experiment Approach.

Microcrystalline cellulose (MCC) of different grades from different manufacturers differ in particulate and powder properties significantly. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this study, the effects of five different MCCs (KG 802, Pharmacel 102, MC 302, M 200, and PH 112) that had different compactibility and tablet disintegration on the tablet quality of two different natural plant products (NPPs) were evaluated systematically, including Crataegi Folium ethanol extract (CF-E) and Sarcandrae Herba water extract (SH-W). The result of D-optimal mixture designs demonstrated that KG 802 showed the best ability to improve compression properties and tensile strength, followed by Pharmacel 102, MC 302, and M 200. PH 112 did the weakest. However, MCCs of different grades had no different influence on the disintegration of NPP tablets. Similar results were found in the experiments of the two different NPP powders, suggesting the generalization of the finding. Moreover, KG 802-containing CF-E formulations showed the largest optimum region size, that is, the lowest production risk. The design space sizes of SH-W were hardly sensitive to the change of MCCs, due to the better tabletability. In conclusion, the properties of MCCs could transfer to the high NPP loading (70%) formulations, leading to the variations on the compression properties and tablet quality. The poorer the tabletability of NPP, the more obvious the variation. The result is promising for the use of MCC and the manufacturing of high drug-loading NPP tablets by direct compression.

DESIGN AND IN VITRO EVALUATION OF ACRIVASTINE AS ORODISPERSIBLE TABLET USING DIRECT COMPRESSION METHOD.

OBJECTIVE: The aim: This study aimed to develop mouth-dissolving tablets of Acrivastine, an antihistamine medication, in order to increase its oral bioavailability. PATIENTS AND METHODS: Materials and methods: Different super disintegrants, such as crospovidone, croscarmellose sodium, and sodium starch glycolate, were used to make Acrivastine oral dispersible tablets (ODTs). These super disintegrants were utilized in various concentrations. The formulation (F3) with 6% w/w crospovidone had a fast disintegration time (less than 30 seconds) and practically total drug release within 10 minutes. All of the formulations were made using the direct compression method and proper diluents, binders, and lubricants. Fourier transform infrared spectroscopy (FTIR) tests were used to investigate the drug-ex¬cipient interaction, and all formulations demonstrated improved drug-excipient compatibility. RESULTS: Results: The average weight of all formulations was between 175 and 180 mg. All formulations' hardness and friability were within acceptable ranges. Direct compression tablets had a hardness of 3.2 to 4 kg/cm2. All formulations were determined to have a friability of less than 1.0%. For oral dissolving tablets, the in vitro disintegration time is critical, and this time preferred to be < 60 seconds. The results also showed that crospovidone disintegrated after 24 seconds and sodium starch glycolate disintegrated in 40 seconds in vitro. CONCLUSION: Conclusions: When compared to croscarmellose sodium and sodium starch glycolate, crospovidone performs better as a super disintegrant. In comparison to other formula, tablets breakdown in the mouth in 30 seconds and have a maximum in vitro drug release time in 1-3 minutes.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (â ¡): classification of tablets disintegration behavior].

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Enrichment of hydrogen production from fruit waste biomass using ozonation assisted with citric acid.

In this study, the impact of ozonation abetted with the citric acid pretreatment (OZCAP) method on fruit waste was investigated for ameliorating hydrogen production. Initially, the ozonation pretreatment (OZP) method was performed by varying ozone (O3) dosage and disintegration time. At optimized conditions (O3 dosage (0.04 g/g suspended solid; SS) and disintegration time (40 minutes)), 17.6% of liquefied organics emancipate rate (LER) and 13.5% of SS reduction were perceived. Further augmenting LER of fruit waste, OZCAP method was proceeded by varying citric acid dosage and disintegration time at an optimized OZP dosage (0.04 g/g SS). A higher LER (24.4%) and SS reduction (19%) were described at an optimal citric acid dosage (0.03 g/g SS) and disintegration time (20 minutes). Then, the hydrogen production potential of OZCAP, OZP and raw fruit waste were evaluated in which OZCAP method exhibited a higher cumulative hydrogen production (30 mL/g volatile solids). Energy valuation reveals that OZCAP method exhibited a net energy of 3.7 kWh/kg of fruit waste.

Investigation of the effects of different beverages on the disintegration time of over-the-counter medications in Saudi Arabia.

Full disintegration of Oral solid dosage forms is critically important to achieve reliable clinical performance of the drug. Tablets/capsules are supposed to be taken with a full glass of water; however, many patients do not follow this recommendation as they administer their medications with beverages other than water. This study aims to assess the impact of different commonly consumed beverages in Saudi Arabia on the disintegration times of common over-the-counter (OTC) medication tablets and capsules in the Kingdom of Saudi Arabia. Five immediate release OTC drugs were chosen: Fevadol®, Solpadeine®, Ralaxon®, Artiz ®, and Brufen®. The disintegration times of these medications were assessed using a disintegration test in five beverages: Coca-cola, arabic coffee, orange juice, buttermilk and an energy drink. Times were compared to the disintegration time in water under two temperature conditions (37 °C and 5 °C). All beverages significantly increased the disintegration times of fevadol, solpadeine, and relaxon in comparison with water. The same was found for burfen, except that arabic coffee did not significantly increase disintegration time (p > 0.05). The disintegration time of artiz tablets was also significantly influenced by all beverages, except for Coca-cola and the energy drink, which had no significant impact on the disintegration time. The tested beverages should not be used as substitutes for water when ingesting medications. Patients should be advised to avoid consuming beverages other than water with therapeutic products. Increasing public awareness of drug-beverage interactions is needed.

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.

Development of probiotic orodispersible tablets using mucoadhesive polymers for buccal mucoadhesion.

OBJECTIVE: Probiotic bacteria, such as different lactobacilli strains, have successfully been used to treat gingivitis and periodontitis or caries. By formulating probiotics as orodispersible tablet (ODT), the benefits of this dosage form could be utilized. Without any further measures, the probiotic bacteria will be eliminated too fast from the intended site of action, the oral mucosa. The use of mucoadhesive granules, composed of mucoadhesive polymer and probiotics, is a promising strategy to prolong the contact time between lactobacilli and oral mucosa without delaying disintegration. METHODS: Three common mucoadhesive polymers, anionic Carbopol 971P NF, nonionic Metolose 65SH50 and cationic chitosan were included into tablets either by direct compression (DC) or after granulation with the probiotics. Disintegration, mucoadhesion of the tablets, and storage stability of the probiotics were characterized. RESULTS: By incorporating a sufficient amount of polymer superior probiotic mucoadhesion could be achieved. All formulations based on granulated probiotics and mucoadhesive polymer fulfilled the Food and Drug Administration (FDA) acceptance level for disintegration of orodispersible tablets. These formulations exhibited excellent storage stability under refrigerated conditions over 30 months. Interestingly, ODTs including Carbopol 971P NF still proved superior mucoadhesion after long-term storage, whereas the mucoadhesive effect of Metolose 65SH50 and chitosan declined markedly. CONCLUSIONS: The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.

[Real time release testing of disintegration time of uncoated Tianshu Tablets].

In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D_c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D_c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D_c+3.59×%H-5.29×%H×D_c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3)<D_c<0.63 g·cm~(-3) and 4.77<%H<7.59 according to the design space. The RTRT model of the disintegration time reflects the understanding of the process system, and lays a foundation for the implementation of intelligent control strategy of the key process of Tianshu Tablets.

Combination of a hot-melt subcoating and an enteric coating for moisture protection of hygroscopic Sennae fructus tablets.

The objective of this study was to investigate the efficiency of moisture protection of hot-melt coatings solely and in combination with an enteric coating on hygroscopic tablet cores containing a spray-dried Sennae fructus extract. Tablet cores were subcoated with different hot-melt coating materials: medium chain tryglycerides, stearic acid, Precirol® ATO 5, and Compritol® 888 ATO, at varying amounts and coated with Eudragit® L 30D-55 for enteric resistance. Subcoating penetration, tablet disintegration, dissolution times, tablet hygroscopicity, and tablet properties such as weight, height, diameter, and hardness were analyzed. 3 mg/cm2 of tablet surface seemed to be sufficient if sustained release is not required. Thereby, hot-melt coating did not adversely affect the tablet properties with regard to subsequent processing steps. Compared to the tablet cores it was possible to reduce the moisture uptake by 85% at 75% relative humidity with tablets coated with a combination of Precirol® ATO 5 and Eudragit® L 30D-55. This combination was more efficient than high amounts of Eudragit® L 30D-55. Hot-melt coating proved to be a suitable technique for the application of subcoating material to tablet cores serving as a barrier against water permeation into hygroscopic tablet cores without exceeding the required disintegration times.

Investigation of the tableting behavior of Ibuprofen DC 85 W.

The aim of the present study was to investigate the tableting behavior of Ibuprofen DC 85 W with special focus on the tablet disintegration time, the tablet crushing strength, and the sticking tendency to punch surfaces. To simulate production conditions, tableting was conducted on a rotary press, equipped with three compaction stations. An I-optimal design of experiments was used to analyze the influence of the pre-compaction, the intermediate compaction, and the main compaction force on the two responses: tablet disintegration time and crushing strength. It was shown that Ibuprofen DC 85 W showed a good tableting behavior with regard to both responses. The tablet disintegration was considerably affected by the maximum compaction force applied, but was also slightly affected by preceding compaction events. The tablet crushing strength was mainly affected by the maximum applied compaction force independent of the order of these forces. The sticking tendency of Ibuprofen DC 85 W was compared with that two other ibuprofen powder formulations in long-term tableting runs. Compared to the other two formulations, sticking was considerably lower with Ibuprofen DC 85 W. The sticking tendency was not influenced by the addition of an intermediate compaction force, but was remarkably reduced by the choice of the punch tip coating.

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X1) mannitol/microcrystalline cellulose ratio, (X2) the amount of low-substituted hydroxypropylcellulose and (X3) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

Understanding the compaction behaviour of low-substituted HPC: macro, micro, and nano-metric evaluations.

The fast development in materials science has resulted in the emergence of new pharmaceutical materials with superior physical and mechanical properties. Low-substituted hydroxypropyl cellulose is an ether derivative of cellulose and is praised for its multi-functionality as a binder, disintegrant, film coating agent and as a suitable material for medical dressings. Nevertheless, very little is known about the compaction behaviour of this polymer. The aim of the current study was to evaluate the compaction and disintegration behaviour of four grades of L-HPC namely; LH32, LH21, LH11, and LHB1. The macrometric properties of the four powders were studied and the compaction behaviour was evaluated using the out-of-die method. LH11 and LH22 showed poor flow properties as the powders were dominated by fibrous particles with high aspect ratios, which reduced the powder flow. LH32 showed a weak compressibility profile and demonstrated a large elastic region, making it harder for this polymer to deform plastically. These findings are supported by AFM which revealed the high roughness of LH32 powder (100.09 ± 18.84 nm), resulting in small area of contact, but promoting mechanical interlocking. On the contrary, LH21 and LH11 powders had smooth surfaces which enabled larger contact area and higher adhesion forces of 21.01 ± 11.35 nN and 9.50 ± 5.78 nN, respectively. This promoted bond formation during compression as LH21 and LH11 powders had low strength yield.

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

PURPOSE: The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. METHODS: Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. RESULTS: The disintegration time (R 2 = 0.86) and API dissolved after 15 min (R 2 = 0.96) linearly correlates with the effective refractive index, n eff, measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff, we observed a better correlation with dissolution after 20 min (R 2 = 0.96) and a weaker correlation with disintegration (R 2 = 0.83) compared to n eff. CONCLUSION: The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.

Comparative study of different approaches for preparation of chlorzoxazone orodispersible tablets.

CONTEXT: Muscle spasm is a painful involuntary contraction of muscles, which causes involuntary movement and distortion. Chlorzoxazone is a centrally acting muscle-relaxant with sedative properties, but given orally, it is hepatically metabolized leading to decreased bioavailability. OBJECTIVE: Orodispersible tablets (ODTs) of chlorzoxazone were formulated using two different approaches; by coprocessed excipients (CE) or by liquisolid (LS) technique. MATERIALS AND METHODS: Pharmaburst® 500, Starlac®, Pearlitol flash®, Prosolv® odt and F-melt® were used as coprocessed superdisintegrants, whereas in LS, Avicel® PH101, Microcelac® 100 and Cellactose® 80 were used as carriers, while Aerosil® 200 was the coating material. ODTs were evaluated in terms of weight and thickness variations, drug content, hardness, friability, wetting time, dissolution, disintegration time (DT) and palatability. RESULTS: In vitro DT of CE-ODTs ranged from 26.43 ± 1.693 s to >180 s, whereas it was between 25.42± 0.203 s to >180 s in LS-ODTs. Complete drug release within 15 min was attained by CE1 prepared with 92.5 mg Pharmaburst® 500. In vivo DT of CE1 and LS3 were 19.779 ± 0.810 and 18.105 ± 0.423 s, respectively, using six volunteers. Volunteers found that CE1 had more acceptable taste and was more palatable than LS3. CONCLUSION: It was concluded that chlorzoxazone ODTs could be successfully formulated using either CE or LS techniques and be used as novel dosage forms for pediatrics and geriatrics showing improved drug release. Moreover, CE technique was superior to LS technique in terms of palatability.

Evaluation of disintegrants functionality for orodispersible mini tablets.

OBJECTIVE: This work evaluates the functionalities of different superdisintegrants (SD) for manufacturing orodispersible mini tablets (ODMT) by direct compression. METHODS: Twenty-three formulations varying in SD type, concentration, and lubricant were used to manufacture ODMT. The ODMT were then characterized for the following properties: friability, porosity, tensile strength, in vivo and in vitro disintegration time (DT). RESULTS: The results show that the presence, type, and concentration of SD did not influence friability, porosity, or tablet tensile strength. With regards to in vivo DT, only cross-linked poly (vinyl pyrrolidone) improved DT in all the tested formulations. Results also showed that when using microcrystalline cellulose (MCC) above 20% in the formulation, DT is longer. Cross-linked carboxymethyl cellulose accelerates DT when the MCC content is less than 20%. As for cross-linked carboxymethyl starch and calcium alginate showed no improvement on DT. Results for in vitro DT were all shorter than in vivo results and there was no correlation with the in vivo evaluation. CONCLUSIONS: This study shows that there is a need to develop better in vitro testing that precisely simulates in vivo conditions and that are adapted to ODMT. This standardization of the test methods for ODMTs must be accompanied by an improvement in the comprehension of SD mechanisms.

The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

CONTEXT: The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. OBJECTIVE: The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). MATERIALS AND METHODS: LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. RESULTS AND DISCUSSION: All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. CONCLUSION: Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.