Crushed Tablet Formulations

BACKGROUND: Despite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency. OBJECTIVE: We summarized current standards of clinical practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency. RESULTS: Fifty-one children were investigated...

Certain patient populations, including children, the elderly or people with dysphagia, find swallowing whole medications such as tablets and capsules difficult. To facilitate oral administration of drugs in such patients, a common practice is to sprinkle the drug products (e.g., usually after crushing the tablet or opening the capsule) on food vehicles before consumption which improves swallowability. Thus, evaluation of the impact of food vehicles on the potency and stability of the administered drug product is important...

BACKGROUND: Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and characterization of SEDDS-based tablets for simvastatin using castor and olive oils as solvents and Tween 60 as surfactant. METHODS: The liquids were adsorbed on microcrystalline cellulose, and all developed formulations were compressed using 10.5 mm shallow concave round punches. RESULTS: The resulting tablets were evaluated for different quality-control parameters at pre- and postcompression levels...

BACKGROUND: While super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice many different LPV/r dosing strategies are applied due to poor availability of paediatric separate ritonavir formulations needed to super-boost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB)-treatment...

OBJECTIVE: To assess the practices and dose uniformity of tablet splitting at selected public hospitals in Northwest Ethiopia. METHODS: A hybrid study method was employed to see the overall practices of tablet splitting. A prospective cross-sectional study was conducted to explore the practices of tablet splitting by administering structured questionnaires to patients and pharmacy professionals. Experimental data on dose and content uniformity of split tablets were obtained from the results of drugs split by study subjects...

Abuse of opioid drug products is a national health crisis in the US. To deter abuse, a number of drug products with abuse-deterrent (AD) properties have been approved by the US Food and Drug Administration (FDA). For abuse deterrence, it is critical to maintain the AD properties during the product shelf life. However, no information on the stability of AD properties during product shelf life is publicly available. In this study, stability of AD properties of surrogate AD formulation (ADF) of opioid active pharmaceutical ingredients (APIs) were studied...

BACKGROUND: Pretomanid (PMD) tablets are indicated as part of a combination regimen for the treatment of adults with pulmonary extensively drug-resistant, treatment-intolerant or non-responsive multidrug-resistant TB. No commercial liquid formulation is currently available for patients unable to swallow these tablets. OBJECTIVE: To develop stable extemporaneous liquid formulations of PMD that can be stored at room temperature or 30°C for at least 4 weeks. METHODS: Crushed PMD tablets were formulated into 20 mg/mL suspensions in a simple syrup and sugar-free formulation...

OBJECTIVE: Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem prodrug of the active agent tebipenem with broad-spectrum activity against drug-resistant Enterobacterales. This study aimed to evaluate the relative bioavailability of crushed tebipenem tablets administered via nasogastric tube (NGT) with or without concomitant enteral feeds. METHODS: This Phase 1, open label study randomized 12 healthy subjects to receive a crushed tebipenem tablet via NGT (n = 6) or via NGT with concomitant Osmolite® enteral feeds (n = 6) on Study Day 1, followed by oral administration of tebipenem whole tablet (reference formulation) on Study Day 2...

Hydroxychloroquine sulfate (HCQS) was granted US-FDA approval in 1955 for the prevention and treatment of malaria. Since then, its uses have expanded to treat systemic lupus erythematosus and rheumatoid arthritis.  For each indication, HCQS is a crucial option for the treatment of pediatric, juvenile, adult, and elderly populations. Existing currently on the market are only 200-mg strength tablets exclusively for adult administration. To facilitate weight-based administration for pediatric and juvenile patients, an HCQS suspension is made by compounding a 200-mg HCQS tablet and suspending the crushed granules into water and Ora-Plus®...

The COVID-19 pandemic outbreak has been overwhelming the healthcare system worldwide. A rapidly growing number of younger pediatric patients in Thailand necessitated the formulation of favipiravir, the most locally accessible antiviral agent against COVID-19, into a child-friendly dosage form as a safer alternative to a dispersion of crushed tablets in simple syrup. While striving to quickly develop a liquid formulation that is feasible for any local hospital production units, an oral solution was chosen due to its simplicity...

This study aims to find the effects of high (75%) and low (30%) humidity conditions and its correlation with formulation composition on dissolution kinetics of lamotrigine (LMT) from prepared immediate-release tablets during one- and four-week periods. Two types of fillers microcrystalline cellulose (MCC) or anhydrous lactose (LAC), disintegrant sodium starch glycolate (NaSG, 0.5% or 4%), and lubricant magnesium stearate (MgST, 0.25% or 5%) were used. A three-factor two-stage complete factorial design (23 ) was used to assess the influence of the composition of the tested formulations...

To overcome difficulties in splitting, uneven breaking and inconsistent dosing frequently reported with scored tablets, a novel punch was proposed for the manufacturing of easy breakable tablets (EBTs). In this work, the performance of the EBT punch was investigated vs. a ridged one for traditional breakable tablets (TBTs) using a furosemide powder formulation for orally disintegrating tablets (ODTs). A Face Centered Central Composite Design was applied to investigate the influence of punch type, compaction force, tablet weight and press rotation speed on the mechanical properties of ODTs, their behavior in aqueous fluids and aptitude for splitting...

Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients and pediatric patients with cerebral palsy and is prescribed to pediatric patients at 0.3 to 1.0 mg/kg/dose. Baclofen tablets, an oral drug, are usually administered as a powder in pediatric wards after a formulation change by the pharmacist. However, there is no information about stability and assurance of quality for compounded products. The purpose of this study was to design a 10 mg/g oral powder of baclofen and to investigate the stability and changes in the physical properties of this compounded product...

Developing acceptable medicines for children is a complicated task. Several factors must be considered, including age, physiology, texture preference, formulation, and legal framework among others. In the development of new paediatric medicines, these factors are assessed. However, for older medicines, e.g., prednisolone, acceptability is still a challenge. This study was an open-label randomised three-arm cross-over study investigating different formulations of prednisolone (crushed tablets, whole tablets, and oral solution) in paediatric patients with asthma and asthma-like symptoms...

Orodispersible tablets (ODTs) are pharmaceutical formulations used to obtain fast therapeutic effects, usually recommended for geriatric and pediatric patients due to their improved compliance, bioavailability, ease of administration, and good palatability. This study aimed to develop ODTs with cannabidiol (CBD) phytocannabinoid extracted from Cannabis sativa used in the treatment of Lennox-Gastaut and Dravet syndromes. The tablets were obtained using an eccentric tableting machine and 9 mm punches. To develop CBD ODTs, the following parameters were varied: the Poloxamer 407 concentration (0 and 10%), the type of co-processed excipient (Prosolv® ODT G2-PODTG2 and Prosolv® EasyTab sp-PETsp), and the type of superdisintegrant (Croscarmellose-CCS, and Soy Polysaccharides-Emcosoy® -EMCS), resulting in eleven formulations (O1-O11)...

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children's needs...

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable...

BACKGROUND: Voriconazole (VRCZ) is the first-line therapy for chronic pulmonary aspergillosis and is available in both intravenous and oral formulations. The bioavailability of the oral form is estimated to be over 90% in healthy volunteers. Some drugs are reported to interact with enteral nutrition (EN), but there are few reports about the trough levels of VRCZ during EN therapy. Here, we describe changes in the VRCZ trough levels in a patient receiving continuous EN therapy. CASE PRESENTATION: The patient was a 58-year-old man with esophageal cancer and a history of partial pulmonary resection due to aspergilloma...

BACKGROUND: Powders for oral solutions and suspensions (POS) are commonly used as pediatric oral medicines worldwide, except for Japan. Although global pediatric formulation development accelerates POS importation to Japan without any formulation change, oral solid multiparticulates remain to be the preferred pediatric forms in the country. This study aimed to evaluate the acceptance situation of four typical POS form products (mycophenolate mofetil, sildenafil citrate, valganciclovir hydrochloride, and voriconazole) that were recently approved in Japan...

Soil-transmitted helminthiasis (STH) is among the most common of parasitic infections, affecting vulnerable populations in tropical/subtropical areas globally. In endemic countries, children, a high-risk population, require treatment and preventive interventions. Mebendazole, a WHO-recommended medicine, originally formulated as a tablet that was often crushed for administration to young children unable to swallow it, was reformulated as a chewable tablet. Acceptability is a key aspect for treatment effectiveness in pediatrics...