scholarly journals Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

Polymers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1395 ◽  
Author(s):  
Mohammed S. Algahtani ◽  
Abdul Aleem Mohammed ◽  
Javed Ahmad ◽  
Ehab Saleh
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Cellulose Acetate ◽  
Immediate Release ◽  
Release Profile ◽  
Drug Dissolution ◽  
Coating System ◽  
Propranolol Hcl ◽  
3D Printed ◽  
The Impact

The use of 3D printing techniques to control drug release has flourished in the past decade, although there is no generic solution that can be applied to the full range of drugs or solid dosage forms. The present study provides a new concept, using the 3D printing technique to print a coating system in the form of shells with various designs to control/modify drug release in immediate-release tablets. A coating system of cellulose acetate in the form of an encapsulating shell was printed through extrusion-based 3D printing technology, where an immediate-release propranolol HCl tablet was placed inside to achieve a sustained drug release profile. The current work investigated the influence of shell composition by using different excipients and also by exploring the impact of shell size on the drug release from the encapsulated tablet. Three-dimensional printed shells with different ratios of rate-controlling polymer (cellulose acetate) and pore-forming agent (D-mannitol) showed the ability to control the amount and the rate of propranolol HCl release from the encapsulated tablet model. The shell-print approach also showed that space/gap available for drug dissolution between the shell wall and the enclosed tablet significantly influenced the release of propranolol HCl. The modified release profile of propranolol HCl achieved through enclosing the tablet in a 3D printed controlled-release shell followed Korsmeyer–Peppas kinetics with non-Fickian diffusion. This approach could be utilized to tailor the release profile of a Biopharmaceutics Classification System (BCS) class I drug tablet (characterized by high solubility and high permeability) to improve patient compliance and promote personalized medicine.

scholarly journals A Study Based on Controlled Drug Release by 3D Printed Aloe-Vera Bi-Layer Tablet

2021 ◽  
pp. 522-531
Author(s):  
Anurag Verma ◽  
Piyush Mittal ◽  
Milind S. Pande ◽  
Neelanchal Trivedi
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Integral Functional ◽  
Aloe Vera ◽  
Controlled Drug Release ◽  
Immediate Release ◽  
Aloe Barbadensis ◽  
3D Printed ◽  
Medicinal Properties ◽  
Printing Techniques

Aloe-Vera or Aloe barbadensis (botanical name) is a plant with many medicinal properties and have great importance in Ayurveda. Its leaves are succulent, erect, forming a thick rosette. The internal translucent pulp of Aloe-Vera is bound to a waxy crust or cuticle, and its vascular tissues transport minerals as well as water from the soil. Aloe Vera is being used as a major skin rejuvenating product, although it has varied medicinal properties also. In the present study, an attempt to make a method to create bi-layer tablets of Aloe-Vera, utilizing 3D printing techniques is presented. The method created doesnt affect the integral functional characteristics of the tablet. The method here contains creating an immediate release and sustained release tablet for making the Aloe-Vera to be used directly by the person for its numerous health effects. The tablet is designed so to be consumed by vegans as well since it is completely herbal.

scholarly journals O22 3D printed polyethylene oxide oral doses with innovative ‘radiator-like’ design: impact of molecular weight on mechanical and rheological properties and drug release

2019 ◽  
Vol 104 (6) ◽  
pp. e10.1-e10 ◽  
Author(s):  
M Peak ◽  
K Baj ◽  
A Isreb ◽  
M Wojsz ◽  
I Mohammad ◽  
...  
Keyword(s):  
Molecular Weight ◽  
3D Printing ◽  
Drug Release ◽  
Rheological Properties ◽  
Oral Dosage ◽  
Parallel Plates ◽  
Fused Deposition ◽  
Plate Spacing ◽  
3D Printed ◽  
The Impact

BackgroundDespite regulatory advances, lack of age-appropriate formulations (AAFs) remains a challenge in paediatric practice. 3D-printing of oral dosage forms (ODFs) offers potential for AAFs for children. Optimising drug release from 3D-printed ODFs is an important technological step. Despite the abundant use of polyethylene oxides (PEOs) and their extensive use as an excipient, there have been no previous reports of applying this thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. We assessed the impact of polymer molecular weight (MW) on the mechanical properties of the resultant filaments and their rheological properties. In the FDM 3D printing process, we also tested the effect of an innovative radiator-like design of the ODF on the acceleration of drug release patterns.MethodsBlends of PEO (MW: 100K, 200K, 300K, 600K or 900K) with PEG 6K (plasticiser) and a model drug (theophylline) were prepared by hot-melt extrusion. The resultant filaments were used as a feed for a FDM 3D printer to fabricate innovative designs of ODFs in a radiator-like geometry with inter-connected paralleled plates and inter-plate spacing of either 0.5mm, 1mm, 1.5mm or 2mm.ResultsVarying blends of PEO and PEG allowed formation of mechanically resistant filaments (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with 100K, 200K, 300K, 600K or 900K, respectively). Filaments of PEO at a MW of 200K-600K were compatible with FDM 3D printing. Further increase in PEO MW resulted in elevated shear viscosity (>104 Pa.S) at the printing temperature and hindered material flow during FDM 3D printing. A minimum spacing (1 mm) between parallel plates of the radiator-like design was essential to boost drug release from the structure.ConclusionThese findings are essential in the development of next-generation personalised drug delivery doses using specialised polymer/polymer blends purposely optimised for FDM 3D printing.Disclosure(s)Nothing to disclose

scholarly journals 3D Printed Microfluidic Devices for Drug Release Assays

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 13
Author(s):  
Benzion Amoyav ◽  
Yoel Goldstein ◽  
Eliana Steinberg ◽  
Ofra Benny
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Particle Production ◽  
Cost Effective ◽  
Drug Dissolution ◽  
Cytotoxicity Test ◽  
High Durability ◽  
One Step ◽  
Cost Effective Alternative ◽  
Multiple Recycling

Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on a 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional “batch” or microfluidic method, based on an optimized solid-in-oil-in-water protocol. Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the “V” shape barrier was similar to that of the dialysis sac test and differed from the “basket” barrier design. Importantly, a cytotoxicity test confirmed biocompatibility of the printed resin. Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication.

scholarly journals Microstructural Control of Polymers Achieved Using Controlled Phase Separation During 3D Printing with Oligomer Libraries: Dictating Drug Release for Personalized Subdermal Implants

2020 ◽  
Author(s):  
Laura Ruiz-Cantu ◽  
Gustavo Trindade ◽  
Vincenzo Taresco ◽  
Zuoxin Zhou ◽  
Laurence Burroughs ◽  
...  
Keyword(s):  
Phase Separation ◽  
3D Printing ◽  
Drug Release ◽  
Material Properties ◽  
High Throughput Screening ◽  
Ink Jet ◽  
Versatile Tool ◽  
3D Printed ◽  
Subdermal Implants ◽  
Level Of Understanding

<p>Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. In this study, we show that ink jet 3D printing of polymer blends gives rise to controllable phase separation that can be used to tailor the release of drugs. We predicted phase separation using high throughput screening combined with a model based on the Flory-Huggins interaction parameter, and were able to show that drug release from 3D printed structures can be predicted from observations based on single drops of mixtures. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be ‘dialed up’ without any manipulation of geometry. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be exploited, bringing a hitherto unseen level of understanding to emergent material properties of 3D printing.</p>

scholarly journals Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?

2014 ◽  
Vol 17 (2) ◽  
pp. 207 ◽  
Author(s):  
Yady Juliana Manrique-Torres ◽  
Danielle J Lee ◽  
Faiza Islam ◽  
Lisa M Nissen ◽  
Julie A.Y. Cichero ◽  
...  
Keyword(s):  
Drug Release ◽  
Orange Juice ◽  
Immediate Release ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Simulated Gastric Fluid ◽  
Drug Bioavailability ◽  
Thickening Agents

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1872 ◽  
Author(s):  
Rishi Thakkar ◽  
Amit Raviraj Pillai ◽  
Jiaxiang Zhang ◽  
Yu Zhang ◽  
Vineet Kulkarni ◽  
...  
Keyword(s):  
Drug Release ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous State ◽  
Dosage Forms ◽  
Water Soluble ◽  
Patient Specific ◽  
3 Dimensional ◽  
Fused Deposition ◽  
3D Printed ◽  
The Impact

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

scholarly journals Development and Evaluation of Amorphous Oral Thin Films Using Solvent-Free Processes: Comparison between 3D Printing and Hot-Melt Extrusion Technologies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1613
Author(s):  
Jiaxiang Zhang ◽  
Anqi Lu ◽  
Rishi Thakkar ◽  
Yu Zhang ◽  
Mohammed Maniruzzaman
Keyword(s):  
Thin Films ◽  
3D Printing ◽  
Drug Release ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Melt Extrusion ◽  
Physico Chemical ◽  
3D Printed ◽  
Hot Melt

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs.

scholarly journals Formulation and Evaluation of Effects of Superdisintegrants on Immediate Release Tablet of Linagliptin, a DDP-4 Inhibitor

2021 ◽  
Vol 24 (2) ◽  
pp. 168-179
Author(s):  
Tanoy Saha ◽  
Md Mahbubul Alam ◽  
Dilshad Noor Lira ◽  
Abu Shara Shamsur Rouf
Keyword(s):  
Drug Release ◽  
Immediate Release ◽  
Pharmaceutical Journal ◽  
Dosage Forms ◽  
Angle Of Repose ◽  
Drug Dissolution ◽  
Disintegration Time ◽  
Weight Variation ◽  
Tablet Dosage ◽  
Release Tablet

The study aimed to develop and evaluate an immediate-release tablet dosage form of Linagliptin. Different concentrations (ranges 5-10%) of super-disintegrants, Croscarmellose sodium (CCS), and Sodium starch glycolate (SSG) were used to prepare nine tablet dosage forms (F1 to F9) through the direct compression method. The compatibility of the formulations was evaluated by FTIR to reveal any possible drug-excipient interactions and it was proved to be compatible with all formulations. Precompression (bulk density, tapped density, Carr’s index, Hausner’s ratio, and angle of repose) and post-compression parameters (weight variation, hardness, thickness, and friability) were analyzed for all tablets and the results were found satisfactory as well as within limits as per USP guidelines. All the formulated batches (F1 to F9) exhibited disintegration of tablets within 2 minutes, where formulation F9 represented the lowest disintegration time (51±3 sec) which was also found significantly better than the marketed product (310±5 sec). In terms of drug dissolution, 90% of drug release was observed for all nine formulations within 45 minutes and formulation F9 (5% CCS and 5% SSG) illustrated the rapid and highest dissolution rate compared to the marketed one’s, 100% drug release at 20 minutes and 91.77 % drug release at 30 minutes successively. The respective data sets of drug release were mathematically fitted to several kinetic models and for all formulations, drug release pattern obeyed first-order kinetics amongst those, formulation F2 (r2= 0.98), F4 (r2= 0.99), F5 (r2= 0.98), and F9 (r2= 0.97) were found to be best fitted in this kinetic norm. Based on disintegration time and dissolution data comparison to a brand leader market product, F9 was experienced as the best formulation. Furthermore, it was observed that if SSG and CCS were combined, then these two parameters were more improved compared to their separate uses. Thus, incorporation of the optimum amount of super-disintegrants in a formulation showed rapid swelling, faster disintegration as well as ease of dissolution of tablet dosage forms. Bangladesh Pharmaceutical Journal 24(2): 168-179, 2021

scholarly journals Parameters Affecting the Mechanical Properties of Three-Dimensional (3D) Printed Carbon Fiber-Reinforced Polylactide Composites

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2456
Author(s):  
Demei Lee ◽  
Guan-Yu Wu
Keyword(s):  
Mechanical Properties ◽  
Carbon Fiber ◽  
3D Printing ◽  
Three Dimensional ◽  
Fused Deposition Modelling ◽  
Layer By Layer ◽  
Fused Deposition ◽  
Bed Temperature ◽  
3D Printed ◽  
The Impact

Three-dimensional (3D) printing is a manufacturing technology which creates three-dimensional objects layer-by-layer or drop-by-drop with minimal material waste. Despite the fact that 3D printing is a versatile and adaptable process and has advantages in establishing complex and net-shaped structures over conventional manufacturing methods, the challenge remains in identifying the optimal parameters for the 3D printing process. This study investigated the influence of processing parameters on the mechanical properties of Fused Deposition Modelling (FDM)-printed carbon fiber-filled polylactide (CFR-PLA) composites by employing an orthogonal array model. After printing, the tensile and impact strengths of the printed composites were measured, and the effects of different parameters on these strengths were examined. The experimental results indicate that 3D-printed CFR-PLA showed a rougher surface morphology than virgin PLA. For the variables selected in this analysis, bed temperature was identified as the most influential parameter on the tensile strength of CFR-PLA-printed parts, while bed temperature and print orientation were the key parameters affecting the impact strengths of printed composites. The 45° orientation printed parts also showed superior mechanical strengths than the 90° printed parts.

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