Compounding of low-dose pharmaceutical powders using a planetary centrifugal mixer

Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

doi:10.1016/j.jddst.2019.04.007

Cited by 6 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, the carmellose sodium was weighed and added to the vessel. To blend the materials, a vessel with a lid was set in a compounding mixer (NW-N300DS, Beat Sensing Co, Ltd, Shizuoka, Japan), and the mixer (online supplemental file 1 (mixer)) was operated at 1500 rpm for 45 s. 11 A predetermined amount of water was added to the blended powders. For granulation, the vessel was set again in the mixer and rotated at 1500 rpm for 45 s. The granules were subsequently coated with talc by rotating the vessel at 600 rpm for 20 s. Finally, the obtained granules were dried in an oven at 50℃ for 4 hours.…”

Section: Granulation Methodsmentioning

confidence: 99%

Extemporaneous preparation of rifampicin granules from capsules to improve usability

2021

Self Cite

View full text Add to dashboard Cite

Objectives Manipulation of tablets or capsules is frequently carried out in pharmacies to regulate doses for personalised therapy. We proposed the use of reconstructed granules as a suitable, flexible dosage form and developed an on-site granulation method using a compounding mixer. The aim of this study was to demonstrate the feasibility of small-scale preparation of granules in a pharmacy setting. Rifampicin capsules were used as a model medicine because of the associated need for drug desensitisation therapy. Methods The contents of a rifampicin capsule were granulated using a compounding mixer, and small ointment containers (12 mL) with filling rates of 4%, 8%, 12%, and 16% were used as granulation vessels. The obtained granules were examined for particle size distribution, yield, crystal transition, drug dissolution profile, storage stability, and weight loss during dosing. ResultsThe yields increased by >95%, and the span of the particle size distribution decreased to 1.0, as the filling rate increased. The smallest batch size was found to be 0.8 g in a 12 mL vessel. Examination of the resultant granules revealed that granulation did not affect the crystal polymorphism, dissolution profile, or storage stability of rifampicin. Furthermore, the weight loss of the granules during the dosing process was significantly lower than that of the capsule powder content. Conclusions We demonstrated that granules with sufficient quality for clinical use could be extemporaneously prepared using a compounding mixer in pharmacies. This improved the usability of the medicine, preventing weight loss, and making it a suitable alternative formulation for precise personalised pharmacotherapy.

show abstract

Section: Granulation Methodsmentioning

confidence: 99%

Extemporaneous preparation of rifampicin granules from capsules to improve usability

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…4) Although the PCM has many advantages over other mixing machines for blending materials, it has only been used for kneading ointments in clinical settings. 5,6) Recently, we reported the feasibility of using a PCM for producing uniform powder blends [7][8][9] free from cross-contamination due to use of disposable vessels. 10) However, use of a PCM for small-scale spherical granulation has not been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Small-Scale Spherical Granulation Using a Planetary Centrifugal Mixer

Eda

Miyazaki

Uchino

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who cannot swallow tablets or capsules. In this study, we determined the feasibility of spherical granulation using a planetary centrifugal mixer. A model formulation, 20% ibuprofen (IBP) granules, was prepared using a lactose/cornstarch (7 : 3, w/w) mixture or D-mannitol as diluents, and changes in granule characteristics (mean diameter (d50), distribution range of granule size (span), and yield) were evaluated according to the amount of water added and the granulation time. The amount of water was assessed using the plastic limit value as measured using a digital force gauge. We successfully produced granules, and larger amounts of water and longer granulation times resulted in larger d50 values and smaller span values. The optimal granulation time was 45 s and the optimal water contents were 70 and 67.5% of the plastic limit value for the lactose/cornstarch mixture and D-mannitol, respectively. When compared to commercial 20% IBP granules, powder X-ray diffraction and differential scanning calorimetry analyses showed that the granulation process did not alter the crystallinity of the drug. Thus, this novel granulation method using a planetary centrifugal mixer may be a promising technique for compounding in pharmacies and in pharmaceutical manufacturing.

show abstract

“…Therefore, pharmacists or patients reformulated this drug to solutions in the U.S.A. and EU 16) or powders in Japan. 17) Thus, it was selected as a model medicine for this reformulation study.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy

Miyazaki

Tsuboi

Maruyama

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Dantrolene capsule, an effective therapeutic agent for the treatment of spasticity, is administered to children who cannot swallow the capsule after reformulation into a powder. The powdered drug can alter the specified dosage and it is also difficult to dispense the powdered formulation because of its bulky and sticky nature. To resolve these problems, we reformulated dantrolene capsules into granules using a centrifugal planetary mixer in the pharmacy. The granules containing lactose-cornstarch, D-mannitol, or microcrystalline cellulose as a diluent were examined to determine particle size distribution, flowability, drug content uniformity, and disintegration time. The granules with microcrystalline cellulose were superior to the other forms, owing to their smaller size, good drug content uniformity, and rapid disintegration. We further investigated the usability of the granules in the dispensing procedure (dividing and packing) and in the dosing process (retrieval from package) using the powders as controls. The deviation of the divided amount and loss on dosing were reduced relative to the powders. In addition, drug dissolution properties and storage stability for 12 months were the same as those of the powders. Therefore, we concluded that dantrolene granules are excellent alternatives as an extemporaneous preparation in pharmacies.

show abstract

Compounding of low-dose pharmaceutical powders using a planetary centrifugal mixer

Cited by 6 publications

References 22 publications

Extemporaneous preparation of rifampicin granules from capsules to improve usability

Extemporaneous preparation of rifampicin granules from capsules to improve usability

Small-Scale Spherical Granulation Using a Planetary Centrifugal Mixer

Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy

Contact Info

Product

Resources

About