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CNS Drugs Mar 2023Rimegepant [Nurtec ODT (USA); Vydura (EU)] is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without... (Review)
Review
Rimegepant [Nurtec ODT (USA); Vydura (EU)] is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without aura in adults, and for the preventive treatment of episodic migraine in adults. Rimegepant is available as an orally disintegrating tablet (ODT), which offers convenience and a potentially faster response time than the conventional tablet formulation. In pivotal phase III trials, rimegepant was more effective than placebo at relieving pain and the most bothersome symptom when taken as needed for the acute treatment of migraine. Rimegepant was also more effective than placebo at reducing the number of monthly migraine days when taken every other day for the preventive treatment of migraine. The beneficial effects of rimegepant in reducing migraine frequency and improving quality of life were maintained over the longer term (up to 52 weeks). Rimegepant was generally well tolerated, with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials. As the first dual agent approved for both treatment and prevention of migraine, rimegepant represents a useful option for the management of migraine in adults.
Topics: Adult; Humans; Quality of Life; Calcitonin Gene-Related Peptide Receptor Antagonists; Migraine Disorders; Tablets
PubMed: 36739335
DOI: 10.1007/s40263-023-00988-8 -
International Journal of Pharmaceutics Oct 2022Recent years have seen the advent of Quality-by-Design (QbD) as a philosophy to ensure the quality, safety, and efficiency of pharmaceutical production. The key...
Recent years have seen the advent of Quality-by-Design (QbD) as a philosophy to ensure the quality, safety, and efficiency of pharmaceutical production. The key pharmaceutical processing methodology of Direct Compression to produce tablets is also the focus of some research. The traditional Design-of-Experiments and purely experimental approach to achieve such quality and process development goals can have significant time and resource requirements. The present work evaluates potential for using combined modelling and experimental approach, which may reduce this burden by predicting the properties of multicomponent tablets from pure component compression and compaction model parameters. Additionally, it evaluates the use of extrapolation from binary tablet data to determine theoretical pure component model parameters for materials that cannot be compacted in the pure form. It was found that extrapolation using binary tablet data - where one known component can be compacted in pure form and the other is a challenging material which cannot be - is possible. Various mixing rules have been evaluated to assess which are suitable for multicomponent tablet property prediction, and in the present work linear averaging using pre-compression volume fractions has been found to be the most suitable for compression model parameters, while for compaction it has been found that averaging using a power law equation form produced the best agreement with experimental data. Different approaches for estimating component volume fractions have also been evaluated, and using estimations based on theoretical relative rates of compression of the pure components has been found to perform slightly better than using constant volume fractions (that assume a fully compressed mixture). The approach presented in this work (extrapolation of, where necessary, binary tablet data combined with mixing rules using volume fractions) provides a framework and path for predictions for multicomponent tablets without the need for any additional fitting based on the multicomponent formulation composition. It allows the knowledge space of the tablet to be rapidly evaluated, and key regions of interest to be identified for follow-up, targeted experiments that that could lead to an establishment of a design and control space and forgo a laborious initial Design-of-Experiments.
Topics: Chemistry, Pharmaceutical; Drug Compounding; Models, Theoretical; Powders; Tablets; Tensile Strength
PubMed: 35987318
DOI: 10.1016/j.ijpharm.2022.122116 -
Therapeutic Delivery May 2020Tablet splitting is a practice disseminated among health professionals for dose adjustments, swallowing facilitation or even treatment cost reduction. Nevertheless,...
Tablet splitting is a practice disseminated among health professionals for dose adjustments, swallowing facilitation or even treatment cost reduction. Nevertheless, tablets not designed for this purpose cause imprecise dosage and stability loss with important therapeutic repercussions. Novel technologies of modified drug release tablets have come to market including new materials and innovative production processes, for example, polymeric matrix, orodispersible, 3D printing, MUPs, etc. The heterogeneity and complexity of these tablets go well beyond a traditional gastroresistant coating tablet, making orientations on the practice of tablet subdivision difficult. This editorial aims to provide a critical and up-to-date evaluation of this scenario based on the most recent studies involving the subdivision of modified-release tablets.
Topics: Polymers; Printing, Three-Dimensional; Tablets
PubMed: 32024453
DOI: 10.4155/tde-2020-0006 -
The Oncologist Jun 2018Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic mutations who have... (Review)
Review
UNLABELLED
Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic mutations who have received three or more prior lines of chemotherapy for maintenance treatment of recurrent OC that is in response to platinum-based chemotherapy regardless of mutation status and for human epidermal growth receptor factor 2-negative metastatic breast cancer with deleterious or suspected deleterious germline mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Because olaparib is poorly soluble and requires advanced drug delivery techniques to ensure bioavailability, the originally approved 400 mg dose is taken as eight 50 mg capsules twice daily. An alternative melt-extrusion tablet formulation was developed to improve the pharmacokinetic and pharmacodynamic profile of olaparib and reduce the pill burden for patients. The recommended tablet dose is 300 mg twice daily (two 150 mg tablets). Phase III studies with the tablet formulation are ongoing for multiple tumor types. Two studies conducted with the olaparib tablet formulation have reported results: one in platinum-sensitive, -mutated recurrent OC (SOLO-2) and one that included patients with germline -mutated metastatic breast cancer (OlympiAD). The tablet is the approved formulation based on the SOLO-2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC. Prior to implementing any changes in therapy, health care providers should engage their patients in discussion to support an informed transition between the formulations.
IMPLICATIONS FOR PRACTICE
Olaparib has recently been approved for maintenance treatment of recurrent ovarian cancer (OC) that is in response to platinum-based chemotherapy. The originally approved capsule formulation was dosed as 400 mg twice daily (eight 50 mg capsules). The recommended olaparib tablet dose is 300 mg twice daily (two 150 mg tablets). The tablet is the new approved formulation based on the SOLO-2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC.
Topics: Antineoplastic Agents; Female; Humans; Ovarian Neoplasms; Phthalazines; Piperazines; Tablets
PubMed: 29593098
DOI: 10.1634/theoncologist.2017-0485 -
International Journal of Pharmaceutics Apr 2021The design and manufacture of tablets is a challenging process due to the complex interrelationships between raw material properties, the manufacturing settings and the...
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.
Topics: Drug Compounding; Excipients; Lactose; Pressure; Solubility; Tablets
PubMed: 33540006
DOI: 10.1016/j.ijpharm.2021.120221 -
International Journal of Pharmaceutics Apr 2022Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to...
Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500-750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behaviour of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in situ sensing in tablet manufacturing.
Topics: Excipients; Particle Size; Porosity; Tablets; Technology, Pharmaceutical; Terahertz Spectroscopy
PubMed: 35181461
DOI: 10.1016/j.ijpharm.2022.121579 -
Acta Medica Okayama Aug 2021Tablet size and head posture have been reported to affect swallowing of medications, but no previous studies have evaluated their effects in detail. Our aim was to...
Tablet size and head posture have been reported to affect swallowing of medications, but no previous studies have evaluated their effects in detail. Our aim was to investigate for the first time the effect of tablet size and head posture on drug swallowing by endoscopic evaluation in healthy subjects. Round tablets (7 , 10 , 12, and 14 mm in diameter) were swallowed by 15 healthy adults with an endoscope inserted in the neutral, head flex-ion, and head extension positions. Evaluation of swallowing difficulty using a numeric rating scale (NRS), presence or absence of pharyngeal residue and its location, and tablet oral transit time (TOTT) were recorded. In the neutral position, the NRS score was higher with the 14 mm tablets than with the 7 mm tablets. The TOTT with the 7 mm tablets was significantly shorter in the head extension than in the neutral position. Swallowing difficulty increased when the tablet diameter was more than 7 mm. Residues were found in the epi-glottis, pyriform sinus, and tongue base. These findings suggest that head extension shortens the TOTT and assists oral-pharyngeal transport.
Topics: Adult; Deglutition; Endoscopy; Female; Healthy Volunteers; Humans; Male; Posture; Tablets
PubMed: 34511617
DOI: 10.18926/AMO/62402 -
The Journal of Allergy and Clinical... Aug 2023Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass...
BACKGROUND
Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet.
OBJECTIVE
We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet.
METHODS
The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects.
RESULTS
Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite-specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets.
CONCLUSIONS
These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.
Topics: Animals; Humans; Retrospective Studies; Rhinitis, Allergic; Allergens; Sublingual Immunotherapy; Anaphylaxis; Poaceae; Dust Mite Allergy; Tablets; Treatment Outcome
PubMed: 36871918
DOI: 10.1016/j.jaci.2023.02.024 -
Chemical & Pharmaceutical Bulletin 2022Mini-tablets (MTs) contain a small amount of active pharmaceutical ingredients in one small tablet. MTs are advantageous because they can be fine-tuned according to the...
Mini-tablets (MTs) contain a small amount of active pharmaceutical ingredients in one small tablet. MTs are advantageous because they can be fine-tuned according to the age and weight of pediatric patients and they are easy for children and the elderly to swallow. However, there are manufacturing concerns such as the difficulty in achieving both hardness and disintegration of a small tablet and it is difficult to keep the tablet weight and drug content consistent in MTs because the mold used for its production is special. In this study, we aimed to determine if an additive such as cellulose nanofibers (CNF), which has been studied in various fields in recent years, could be used to manufacture MTs without difficulties. In this study, an MT was manufactured using a rotary tableting press with a compression force of 2, 5, and 8 kN, and the weight variation, drug content variation, tensile strength, friability, disintegration time, and drug dissolution were evaluated. Of note, the tensile strength of MTs produced with a compression force of ≥5 kN was ≥1.3 MPa, which was comparable to that of an ordinary tablet with an 8 mm diameter and a hardness of ≥30 N. The disintegration time of the MT which was 20-30% CNF was ≤30 s at any compression force. MTs with CNF showed similar disintegration to MTs with other common disintegrants. Therefore, we found that CNF is a functional additive capable of manufacturing MTs by direct powder compression which has both strength and disintegration.
Topics: Aged; Cellulose; Child; Drug Compounding; Hardness; Humans; Nanofibers; Powders; Tablets; Tensile Strength
PubMed: 36047234
DOI: 10.1248/cpb.c22-00290 -
European Journal of Pharmaceutics and... Nov 2022Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The...
Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The current research aims to model the impact of lactose properties on disintegration time. For the first time, the impact of lactose polymorphism, tablet tensile strength, and pore structure parameters on disintegration were evaluated in one study. Six different lactose qualities were compacted into tablets of different solid fractions in a formulation with 5 %w/w diclofenac sodium, 1 %w/w magnesium stearate and 2 %w/w croscarmellose sodium. A linear model was built to identify which parameters impact the disintegration time, using as potential variables the polymorphic composition of the lactose, the porosity, pore size distribution and the tablet tensile strength. The model variables were derived from literature and calibrated with data. After optimization, the model shows a strong correlation (r = 0.982) between measured and predicted disintegration times. Among all investigated variables, the polymorphic composition of lactose, and the pore size distribution have been identified to affect tablet disintegration most. A higher concentration of lactose monohydrate in tablets leads to faster tablet disintegration, explained by the slower dissolution rate of lactose monohydrate compared to anhydrous and amorphous lactose. Tablet tensile strength was not identified as a direct driver for disintegration. Instead, the pore size distribution is a mutual driver for both tablet tensile strength and disintegration. The obtained insights provide guidance on the importance of quality attributes of filler binders for the prediction of tablet disintegration. This study can therefore be used as a starting point for quality-by-design formulation development and for the development of mechanistic models to predict tablet disintegration.
Topics: Lactose; Porosity; Solubility; Tablets; Excipients
PubMed: 36270465
DOI: 10.1016/j.ejpb.2022.10.012