System and method for fabrication of uniform polymer films containing nano and micro particles via continuous drying process
Inventors
Dave, Rajesh N. • Susarla, Ramani • Khusid, Boris • Bhakay, Anagha A. • Bilgili, Ecevit A. • Muzzio, Fernando
Assignees
New Jersey Institute of Technology • Rutgers State University of New Jersey
Publication Number
US-10646452-B2
Publication Date
2020-05-12
Expiration Date
2034-03-17
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Abstract
The present disclosure provides improved stripfilm based pharmaceutical products (e.g., for enhancing dissolution and bioavailability). More particularly, the present disclosure provides improved systems/methods for fabricating stripfilm based pharmaceutical products by utilizing higher viscosity film forming precursors and drying methods that accomplish improved/faster drying and provide improved/excellent content uniformity of active pharmaceutical agents in the stripfilm based pharmaceutical products. Exemplary systems/methods advantageously use high viscosity, bio-compatible polymeric precursors, (optional use of surface modified drug powders), and convective drying for fabrication of thin films loaded with nano and/or micro sized particles of poorly water-soluble active pharmaceutical ingredients (APIs) to achieve improved active content uniformity and very fast dissolution from poorly water soluble actives, while accomplishing fast drying during the fabrication process. The present disclosure provides for the fast drying (e.g., via low temperature forced convection) of biocompatible polymer films loaded with poorly water-soluble drug nano-particles.
Core Innovation
The invention provides improved stripfilm based pharmaceutical products designed to enhance dissolution and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). It presents advanced systems and methods for fabricating such stripfilms by employing higher viscosity film forming precursors combined with drying methods that achieve improved and faster drying and result in excellent content uniformity of active agents within the stripfilms. Exemplary embodiments utilize high viscosity, biocompatible polymeric precursors and apply convective drying techniques to fabricate thin films loaded with nano and/or micro sized particles of poorly water-soluble APIs.
The problem being addressed is the challenge of maintaining drug content uniformity and preserving the crystalline form of poorly water-soluble APIs when incorporated into thin films. Existing fabrication methods such as hot melt extrusion and solvent casting often face limitations, including difficulty preserving API crystalline forms, long drying times, and high temperature conditions unsuitable for heat sensitive drugs. Moreover, prior art lacks discussion about forming films based on nano or micro particles of poorly water soluble drugs with excellent content uniformity and fast drying times, which are critical for manufacturability, stability, and therapeutic efficacy.
The disclosure introduces a solvent casting technique utilizing higher viscosity film precursors (ranging from about 100 cP to 25,000 cP, preferably 2,500 cP to 25,000 cP) mixed with active agent nano or micro particles. The mixture is dried under controlled low temperature forced convection, laminar airflow, or combinations of conduction, convection and radiation heating at temperatures ranging from about 0° C. to 80° C., and relative humidity from about 20% to 90%, typically for 10 to 90 minutes. This results in stripfilms with uniform drug particle loading (with relative standard deviation less than 6%), fast drying times, preserved API crystallinity, and ultra-fast dissolution rates. The method allows tailoring of dissolution profiles by adjusting film thickness and polymer composition and supports incorporation of drug particles in crystalline or amorphous forms as suspensions or dry powders.
Claims Coverage
The patent includes multiple independent claims focusing on methods for fabricating pharmaceutical stripfilms. The claims cover various inventive features related to composition, viscosity control, drying conditions, particle size, mixing methods, and dosage uniformity.
Use of high viscosity aqueous film forming precursor compositions containing superdisintegrants
Method involves providing an aqueous film forming precursor composition that includes superdisintegrants which increase the viscosity of the mixture to about 100 cP to 25,000 cP prior to forming a stripfilm.
Mixing with active agent nanoparticles and forming a suspension
Mixing the aqueous film forming precursor composition containing superdisintegrants with active agent nano-particles to form a uniform suspension or mixture prior to casting or drying.
Drying under controlled temperature and humidity conditions
Drying the mixture at low temperatures ranging from about 0° C. to 80° C. and relative humidity between about 20% to 90%, using techniques including convective drying in laminar flow conditions, to form the stripfilm in 10 to 90 minutes.
Flexibility in particle size and particle form of active agent
Incorporation of active agent nano-particles or micro-particles with particle size ranging from about 5 nm to 20,000 nm, and active agent particles being crystalline, amorphous, or a combination thereof.
Maintaining drug content uniformity and water content
Producing films having active agent loading uniformity with relative standard deviation less than about 6%, and films containing 5% to 8% water by weight.
Mixing technologies to ensure homogeneity
Use of vibratory or planetary mixers operating at various accelerations and speeds to achieve homogeneous mixing and dispersal of nanoparticles within viscous polymer precursors.
Redispersion of nanoparticles from films
Capability of re-dispersing the fabricated stripfilm in aqueous medium with nanoparticle size distribution preserved within 20% variation of original particle size, ensuring maintained bioavailability.
Inclusion of various film components and dosage forms
Incorporation of one or more water-soluble or insoluble polymers, surface modifying agents, plasticizers, viscosity enhancers, and formation of multi-layer films or their incorporation into tablets, capsules or patches.
The claims comprise a method of producing pharmaceutical stripfilms with highly viscous aqueous film precursors containing superdisintegrants and active agent nano or micro particles, dried under controlled gentle conditions to achieve films with excellent drug uniformity, rapid dissolution, and preserved particle characteristics. The claims cover details of particle size, drying atmosphere, mixing methods, film composition, and redispersion capabilities, providing a comprehensive fabrication approach enabling improved pharmaceutical stripfilms.
Stated Advantages
Improved and faster drying process leading to reduced manufacturing times of pharmaceutical stripfilms.
Enhanced uniformity of active pharmaceutical agent content within the stripfilms, with low relative standard deviation values even at low doses.
Capability to maintain the crystalline form and the nano/micro particle size distribution of poorly water soluble drugs in the films, preserving drug stability.
Versatility in tailoring drug release profiles, including immediate or sustained release, via modulation of film thickness and polymer composition.
Use of higher viscosity film precursors enables better mixing, film uniformity, and process scalability.
Manufacturing process compatible with heat-sensitive drugs due to use of low to moderate drying temperatures and controlled humidity conditions.
The stripfilm format improves patient compliance and enables cost-effective continuous processing and scale-up.
Documented Applications
Oral, buccal, or sublingual delivery of poorly water soluble drugs via quick dissolving thin polymeric stripfilms.
Dermal patches and skin delivery of active pharmaceutical agents.
Acts as wraps or coatings for biocompatible devices, stents and prosthetics delivering antibiotics, antibacterials, antimicrobials, or anti-pain substances.
Formation of multi-layer film structures for oral dosage forms, including tablets coated or adhered with one or more active ingredient-containing film layers for controlled release.
Incorporation of films into tablets, capsules, and patches as dosage forms or for encapsulation of pharmaceutical or other objects.
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