The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl® 300, Fujisil®, Syloid® 244 FP, Syloid® XDP 3050, Neusilin® S2, Neusilin® US2, and Neusilin® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly.
- Publikační typ
- časopisecké články MeSH
The aim of this study was to prepare benzydamine hydrochloride loaded orodispersible films using modified semisolid extrusion 3D printing method. An innovative approach was developed where thin layer of drug loaded dispersion is printed and dried before printing of subsequent layers. Layer-by-layer drying as the in process step improves mechanical properties of films, uniformity of drug content and allows faster preparation of films in compounding settings due to shortening of drying time. Orodispersible films consisted of film forming maltodextrin, sorbitol as a plasticizer and hydroxyethylcellulose as a thickening agent. The height of the digital model showed excellent correlation with the disintegration time, weight, thickness and mechanical properties of prepared films. Drug content, predefined by volume of digital model and concentration of drug in print dispersion, showed excellent uniformity. The modified printing method shows great promise in a compounding production of personalized film dosage forms, and brings in possibilities such as one step preparation of films with compartmented drugs and incorporation of taste masking or release control layers.
3D printing is a rapidly growing technology. Besides its general industrial application, it is also applicable in manufacturing of dosage forms. Due to its inherent flexibility, it is predetermined to be used as an advantageous manufacturing tool in the clinical phases of the drug development and in the individualized pharmacotherapy. Properties of drug dosage forms, such as the size of the dose, the type of the release mechanism, the shape and colour, can easily be modified and the final form can be produced quickly in small batches. It is also possible to prepare dosage forms with properties unattainable by classic manufacturing.
Warfarin je léčivem s úzkým terapeutickým indexem. Individuální titrace dávky a průběžná kontrola terapie je vyvážena dlouhodobou klinickou praxí a nízkými náklady. S ohledem na nízké dávky je jedním z kritických parametrů obsahová stejnoměrnost pevné lékové formy. Ta musí vyhovět nejen lékopisným požadavkům, ale i na definované statistické hladině významnosti zaručit jejich splnění. Tato práce se zabývá vlivem koncentrace léčiva a časem domísení směsi po přídavku lubrikantu na obsahovou stejnoměrnost směsí a z nich nalisovaných tablet. Výsledky ukazují, že pro dosažení vyhovující obsahové stejnoměrnosti je vhodná koncentrace léčiva 2–2,7 % a její zvýšení nebo snížení má na obsahovou stejnoměrnost negativní vliv. Výsledky rovněž potvrzují čas domísení 5 minut jako adekvátní, neboť při delší homogenizaci dochází k tzv. přemísení směsi.
Warfarin is a drug with narrow therapeutic index. Individualization of dose and thorough therapy monitoring is compensated by long time use in praxis and low therapy cost. Considering the low dose usually administered, critical parameter of solid dosage form is its uniformity of content. It has to not only meet the criteria set by pharmacopoeia, but to meet them on statisticall significant level also. This experimental study asseses impact of warfarin concentration and blending time after adition of lubricant on uniformity of content of mixtures and tablets made of them. It concludes, that concentration in 2–2,7% range is optimal and its increase or decrease has a negative effect on uniformity of content. It also confirms 5 minutes of blending after lubricant addition to be adequate, as employing longer blending times leads to mixture overblending.
