Explore the vast range of titles available.

PurposeOrodispersible 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.MethodsWe 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.ResultsThe 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.ConclusionsWe 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.

Co-processing (CP) provides superior properties to excipients and has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms. Development of directly compressible formulations with high doses of poorly flowing/compressible active pharmaceutical ingredients, such as paracetamol, remains a great challenge for the pharmaceutical industry due to the lack of understanding of the interplay between the formulation properties, process of compaction, and stages of tablets’ detachment and ejection. The aim of this study was to analyze the influence of the compression load, excipients’ co-processing and the addition of paracetamol on the obtained tablets’ tensile strength and the specific parameters of the tableting process, such as (net) compression work, elastic recovery, detachment, and ejection work, as well as the ejection force. Two types of neural networks were used to analyze the data: classification (Kohonen network) and regression networks (multilayer perceptron and radial basis function), to build prediction models and identify the variables that are predominantly affecting the tableting process and the obtained tablets’ tensile strength. It has been demonstrated that sophisticated data-mining methods are necessary to interpret complex phenomena regarding the effect of co-processing on tableting properties of directly compressible excipients.

This study exposes the potential usefulness of a new co-processed excipient, composed of alginic acid and microcrystalline cellulose (Cop AA-MCC), for the preparation of immediate drug release tablets by direct compression. Evaluation of the physical and mechanical properties as well as the disintegration behavior of Cop AA-MCC in comparison to commercial co-processed excipients (Cellactose®, Ludipress®, Prosolv® SMCC HD90 and Prosolv® ODT) and to the physical mixture of the native excipients (MCC and AA), was carried out. The obtained results illustrate the good performance of Cop AA-MCC in terms of powder flowability, tablet tensile strength, compressibility, and disintegration time. Although, this new co-processed excipient showed a slightly high lubricant sensitivity, which was explained by its more plastic than fragmentary deformation behavior, it presented a low lubricant requirement due to the remarkably low ejection force observed during compression. Compression speed and dwell time seemed not to affect significantly the tabletability of Cop AA-MCC. The study exposed evenly the performance of Cop AA-MCC compared to Prosolv® ODT, in terms of tabletability and dissolution rate of Melatonin. Cop AA-MCC presented comparable hardness, lower dilution potential, higher lubricant sensitivity, lower ejection force, and faster Melatonin’s release time than Prosolv® ODT. In summary, Cop AA-MCC exhibited interesting physical, mechanical, and biopharmaceutical properties, which demonstrate its concurrence to commercially available co-processed excipients. Furthermore, the simplicity of its composition and the scalability of its elaboration makes this multifunctional excipient highly recommended for direct compression.

Background/Objectives: Direct compression offers a cost-effective route for tablet manufacturing but is often limited by poor powder flow and compressibility. This study reported the development of a co-processed excipient comprising 98% mannitol and 2% pregelatinized rice starch (PRS) using spray drying with ammonium bicarbonate as a pore-forming agent. Methods: This optimized excipient demonstrated balanced powder flow and enhanced compressibility suitable for direct compression applications. The SeDeM expert system guided the optimization process by evaluating raw and spray-dried components. PRS exhibited excellent flowability that decreased after spray drying but displayed significantly enhanced compressibility, whereas mannitol maintained superior flow but continued to show limited compressibility post-drying. Scanning electron microscopy, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and X-ray powder diffraction confirmed the absence of chemical interactions and unchanged wettability during co-processing. Results: The resulting excipient combined the favorable flow characteristics of mannitol with the improved compressibility of PRS, rendering it suitable for direct compression. Cetirizine dihydrochloride (CET) tablets were formulated via exponential curve fitting within the SeDeM framework, yielding an optimal CET-to-excipient ratio of 13:87. The tablets met all pharmacopeial physicochemical requirements, including uniform mass, adequate tensile strength, rapid disintegration, and dissolution profiles comparable to a reference product, with dissimilarity (f1 = 4.28) and similarity (f2 = 64.03) factors within regulatory acceptance limits. Conclusions: These findings represented the first application of SeDeM methodology to a co-processed mannitol–pregelatinized rice starch system, enabling predictive optimization of powder flow and compressibility in direct compression formulations.

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box–Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved Cmax, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets.

The utilization of co-processed excipients (CPEs) represents a novel approach to the preparation of orally disintegrating tablets by direct compression. Flow, consolidation, and compression properties of four lactose-based CPEs—Cellactose® 80, CombiLac®, MicroceLac® 100, and StarLac®—were investigated using different methods, including granulometry, powder rheometry, and tablet compaction under three pressures. Due to the similar composition and the same preparation technique (spray drying), the properties of CPEs and their compacts were generally comparable. The most pronounced differences were observed in flowability, undissolved fraction after 3 min and 24 h, energy of plastic deformation (E2), ejection force, consolidation behavior, and compact friability. Cellactose® 80 exhibited the most pronounced consolidation behavior, the lowest values of ejection force, and high friability of compacts. CombiLac® showed excellent flow properties but insufficient friability, except for compacts prepared at the highest compression pressure (182 MPa). MicroceLac® 100 displayed the poorest flow properties, lower ejection forces, and the best mechanical resistance of compacts. StarLac® showed excellent flow properties, the lowest amounts of undissolved fraction, the highest ejection force values, and the worst compact mechanical resistance. The obtained results revealed that higher compression pressures need to be used or further excipients have to be added to all tested materials in order to improve the friability and tensile strength of formed tablets, except for MicroceLac® 100.

Background/Objectives: Enhancing excipient functionality through environmentally friendly and scalable processing methods is essential for improving the manufacturability and performance of orally disintegrating tablets (ODTs). Microwave-assisted wet granulation enables controlled microstructural modification without chemical alteration of excipient components. This study aimed to develop and evaluate a rice starch (RS)–mannitol co-processed excipient using microwave-assisted wet granulation for direct compression of ODTs. Methods: RS and mannitol were co-processed by wet granulation followed by microwave treatment under varying power levels and irradiation times. The effects of processing conditions on granule morphology, solid-state properties, porosity, powder flow, compressibility, wettability, and disintegration behavior were systematically investigated. The optimized excipient was further evaluated in ODT formulations containing chlorpheniramine maleate and piroxicam and benchmarked against a commercial co-processed excipient (Starlac®). Results: Microwave treatment generated internal vapor pressure that promoted pore formation and particle agglomeration, resulting in enhanced powder flowability (compressibility index 8.4–10.8%). Partial crystallinity reduction and microstructural modification improved compressibility and surface wettability compared with non-microwave-treated materials. The optimized formulation (MW-RM-H-30) exhibited rapid wetting (25 s), high water absorption (90.5%), low contact angle (42°), and fast tablet disintegration (31 s). ODTs prepared with MW-RM-H-30 showed rapid disintegration (42 s for chlorpheniramine maleate and 32 s for piroxicam) and dissolution behavior comparable to Starlac®. Conclusions: Microwave-assisted wet granulation provides an efficient, scalable, and environmentally friendly strategy for engineering starch-based co-processed excipients with enhanced functionality for direct compression ODT applications. The developed excipient demonstrates strong potential for solid dosage form manufacturing.

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.

This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis. Direct compression method was used to prepare ODTs using three types of co-processed excipients (Prosolv ODT G2 , F-melt , and Pharmaburst 500). ODTs were evaluated according to weight variation, thickness, friability, hardness, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution test, and palatability. To enhance the in-vitro dissolution of meloxicam and palatability of ODT, a six sigma methodology was used, and an improvement phase was established where ODTs were prepared using lyophilization and levigation techniques. Finally, a pharmacokinetic study of the improved ODT was accomplished in comparison to the conventional oral tablet. Pharmaburst-based formula (F4) showed the shortest wetting time and, consequently, the shortest disintegration time and the highest percentage of drug dissolved within 3 min compared to the other formulae. All the improved ODTs had a bitterness taste score vary from (0) palatable and (+1) tasteless. The current sigma level was 3.628 σ and 3.33 σ for palatability and solubility of ODT, respectively, which indicated the process was successfully improved compared with the previous sigma level of 2.342 σ of both processes. Pharmacokinetic study of the improved ODTs showed a significant decrease of T to 120 and 30 min instead of 180 and 120 min for meloxicam and baclofen, respectively. ODTs were successfully improved using the six sigma methodology, the pharmacokinetic parameters of both drugs were enhanced due to rapid absorption through the oral mucosa.

Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy. This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon and Lornoxicam ). Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q . LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma. Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst (F2) had significantly ( <0.05) the fastest DT (6.66±1.52 s) and highest Q (79.07±2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products. The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.