Increased drug load and polymer compatibility of bilayered orodispersible films

Visser, Jan; Weggemans, Oekie A.F.; Boosman, R.; Loos, Katja; Frijlink, Henderik W.; Woerdenbag, Herman J.

doi:10.1016/j.ejps.2017.07.010

Cited by 36 publications

(19 citation statements)

References 19 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Values of %E that are too high (340%-260%), which are observed for AP/PVP films at a low LO load (up to 15% w/w), make it difficult to package or divide the film into single-dose units, due to deformation. Although there are no limits defined for the viscoelastic parameters that correlate with a good performance of ODF during manipulation, our observations and some data reported by other authors may suggest that the values of %E below 100% are usually applicable [41]. For products on the market, values %E below 40% were measured [42].…”

Section: Polymersupporting

confidence: 38%

Technology of Orodispersible Polymer Films with Micronized Loratadine—Influence of Different Drug Loadings on Film Properties

2020

View full text Add to dashboard Cite

The production of orodispersible films (ODFs) with suspended insoluble drug substances is still a challenge, mainly due to the difficulty associated with achieving a proper homogeneity and mechanical properties of the films. Hypromellose (HPMC) and a mixture of polyvinyl alcohol (AP) and povidone (PVP) were compared in terms of their suitability for ODFs incorporating suspended micronized loratadine (LO) in a concentration range of 10%–40%. In a planetary mixer (Thinky), a uniform dispersion of LO in an aqueous viscous casting solution was obtained. The suspended LO particles caused dose-dependent changes in the viscosity of the casting mass and affected the mechanical quality of ODFs. Drug concentrations higher than 30% reduced the film flexibility and tear resistance, depending on the polymer type. LO films with a thickness of 100 µm disintegrated within 60-100 s, with no significant influence of the LO content in the range 10%–30%. HPMC films, regardless of the drug concentration, met the pharmacopoeial requirements regarding the uniformity of the drug content. AP/PVP films were too elastic, and the drug content uniformity was not achieved. The conclusion is that, using an HPMC matrix, it is possible to obtain a high load of a poorly water-soluble drug (30% of dry film mass corresponds to a dose of 5 mg per 1.5 cm2) in ODFs characterized by proper physical characteristics.

show abstract

Section: Polymersupporting

confidence: 38%

Technology of Orodispersible Polymer Films with Micronized Loratadine—Influence of Different Drug Loadings on Film Properties

2020

View full text Add to dashboard Cite

show abstract

“…Little information is available on the ODF stickiness perception as potential acceptability-influencing attribute (Visser et al, 2017). ODF stickiness was mentioned in few works with regards to observations on its potential impact on manufacturing and mechanical properties [42][43][44][45].…”

Section: Texture Analysismentioning

confidence: 99%

Key acceptability attributes of orodispersible films

Scarpa¹,

Paudel

Kloprogge

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the potential to affect the end-user acceptability. ODF stickiness and disintegration time should therefore be evaluated at an early stage of the drug product design.

show abstract

“…The mechanical properties of ODFs with β-galactosidase incorporated and plain ODFs were analyzed using an Instron series 5500 load frames with a load cell of 100 N (Instron, Norwood, USA) [13,18,25]. ODF were cut into a bone shape according to ISO-527 standard (plastics-determination of tensile properties) (NEN-EN-ISO, 2012).…”

Section: Mechanical Propertiesmentioning

confidence: 99%

“…However, such production method would imply quite some waste of vaccine as the edges of the films left after cutting films into the desired shape are usually discarded. To overcome this disadvantage, we used a plain ODF, developed by us in a previous study [13], onto which the vaccine solution containing stabilizers was pipetted followed by air-or vacuum-drying. This procedure enables precise and low volume antigen deposition.…”

Section: Introductionmentioning

confidence: 99%

Development of an Orodispersible Film Containing Stabilized Influenza Vaccine

et al. 2020

Self Cite

View full text Add to dashboard Cite

Most influenza vaccines are administered via injection, which is considered as user-unfriendly. Vaccination via oral cavity using an orodispersible film (ODF) might be a promising alternative. To maintain the antigenicity of the vaccine during preparation and subsequent storage of these ODFs, sugars such as trehalose and pullulan can be employed as stabilizing excipients for the antigens. In this study, first, β-galactosidase was used as a model antigen. Solutions containing β-galactosidase and sugar (trehalose or trehalose/pullulan blends) were pipetted onto plain ODFs and then either air- or vacuum-dried. Subsequently, sugar ratios yielding the highest β-galactosidase stability were used to prepare ODFs containing H5N1 whole inactivated influenza virus vaccine (WIV). The stability of the H5N1 hemagglutinin was assessed by measuring its hemagglutination activity. Overall, various compositions of trehalose and pullulan successfully stabilized β-galactosidase and WIV in ODFs. WIV incorporated in ODFs showed excellent stability even at challenging storage conditions (60 °C/0% relative humidity or 30 °C/56% relative humidity) for 4 weeks. Except for sugars, the polymeric component of ODFs, i.e., hypromellose, possibly improved stability of WIV as well. In conclusion, ODFs may be suitable for delivering of WIV to the oral cavity and can possibly serve as an alternative for injections.

show abstract

Increased drug load and polymer compatibility of bilayered orodispersible films

Cited by 36 publications

References 19 publications

Technology of Orodispersible Polymer Films with Micronized Loratadine—Influence of Different Drug Loadings on Film Properties

Technology of Orodispersible Polymer Films with Micronized Loratadine—Influence of Different Drug Loadings on Film Properties

Key acceptability attributes of orodispersible films

Development of an Orodispersible Film Containing Stabilized Influenza Vaccine

Contact Info

Product

Resources

About