Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique
Аутори
Pešić, NikolaKrkobabić, Mirjana
Adamov, Ivana
Ibrić, Svetlana
Ivković, Branka
Medarević, Đorđe
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
1. INTRODUCTION
When it comes to pharmacy, 3D printing has
gained immense popularity in recent years due
to its revolutionary use in printing drugs tailored
to individual patient needs [1,2]. Selective laser
sintering (SLS) is an industrial 3D printing
technique which uses a powder bed to build up
the 3D object thanks to a laser which binds the
powder particles together. Advantages of SLS
technique include the fact that it is a solvent-free
process and offers relatively fast production.
Until today, a limited number of studies
investigating the production of drug dosage
forms using SLS have been reported [2,3].
2. MATERIALS AND METHODS
2.1. Materials
Carvedilol (CRV) was used as a model
substance in this study and it was donated by
Hemofarm (Vršac, Serbia). The following
excipients used to obtain 3D printing tablets:
polyvinyl alcohol (PVA, Merck), mannitol
(Parteck® M, Merck), Ludipress®
(coprocessed excipient consisting of 93%
lactose monohydrate, 3.5% crospovi...done
(Kollidon® CL) and 3.5% povidone K30
(Kollidon® 30), BASF), talc (Merck) and
candurin (Candurin® Gold Sheen, Merck).
2.2. Preparation of formulations
The compositions of the formulations are
shown in Table 1.
Table 1. Composition of the formulations
Material Formulation 1 Formulation 2
CRV 10% 10%
PVA 55% 55%
Parteck® M 30% /
Ludipress® / 30%
Talc 2% 2%
Candurin®
Gold Sheen 3% 3%
Powder for 3D printing was obtained by mixing
all the components of the formulation and
sifting through a sieve with a diameter of 180
μm.
2.3. 3D printing of oral dosage forms
A cylindrical 3D models of the printed tablets
(8.00 mm diameter and 2.00 mm thickness)
were designed with Autodesk Fusion 360
software version 2.0.8809 (Autodesk Inc, San
Rafael, CA, USA), exported as a
stereolithography file (.stl) and printed with
Sintratec Kit 3D printer (Sintratec AG,
Switzerland). The printing parameters were
controlled using Sintratec 3D printer software.
After a series of variations in temperature and
laser speed, the optimal values of these
parameters used in the 3D printing process were
established and shown in Table 2.
Table 2. SLS 3D printing process parameters
Surface
Temperature
( ◦C)
Chamber
Temperature
( ◦C)
Laser
speed
(mm/s)
Hatch
space
80 ºC 70 ºC 60 250 μm
2.4. Mechanical properties of 3D tablets
Tablets (n = 10) were weighed on a Sartorius BP
210 D analytical balance (Sartorius, Goettingen,
Germany) and measured (diameter and
thickness) using a digital caliper (Vogel,
Kevelaer, Germany).
2.5. Powder X-ray diffraction analysis
(PXRD)
PXRD analysis was performed to assess
whether the laser induced amorphization of any
of the compounds, especially amorphization of
poorly soluble CRV. Samples were collected
using a Philips PW-1050 (Philips, The
Netherlands) diffractometer, operated at 40 kV
and 30 mA, using Ni-filtered Cu Kα radiation.
2.6. Dissolution and Drug Release Analysis
Dissolution testing was performed under nonsink
conditions using mini paddle apparatus
(Erweka DT 600, Germany) with a paddle
rotation speed of 50 rpm for 8 h, in 100 ml of
phosphate buffer (pH 6.8). The amount of
dissolved CRV was determined by HPLC
method using Dionex Ultimate 3000 (Thermo
Scientific, USA) HPLC system.
3. RESULTS AND DISCUSSION
3.1. 3D printing process
It was shown that SLS printer was able to
fabricate 3D tablets with CRV, as well as that
success of the printing process depended on the
used printing parameters.
3.2. Mechanical properties of 3D tablets
The dimensions of the obtained 3D tablets were
in accordance with the defined values of the
created 3D models (F1: 8.10 ± 0.08 mm
diameter and 2.10 ± 0.13 mm thickness, F2:
8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm
thickness). Significant variations in tablet
weight between formulations were not observed
(m1=0.146 ± 0.04; m2=0.136 ± 0.03).
3.3. Powder X-ray diffraction analysis
(PXRD)
Figure 1. The X-ray powder diffraction of F1
and F2.
3.4. Dissolution and Drug Release Analysis
Figure 2. Dissolution profiles of 3D printing
tablets
4. CONCLUSION
SLA represents a new chapter in 3D printing of
solid oral dosage forms and in individualized
therapy in particular. By adjusting the
formulation and process parameters, it was
possible to produce SLS tablets with coamorphous
CRV and PVA as a main polymer.
Complete drug release was achieved under non
sink conditions after 8 hours in phosphate
buffer. The tailoring of drug release might be
achieved by varying formulation factors as well
as process parameters, although it could be
governed by the composition of the whole
formulation.
Извор:
9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts, 2022, 210-211Издавач:
- Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo
Напомена:
- 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow Ljubljana, Slovenia, 15th-17th September, 2022
Институција/група
PharmacyTY - CONF AU - Pešić, Nikola AU - Krkobabić, Mirjana AU - Adamov, Ivana AU - Ibrić, Svetlana AU - Ivković, Branka AU - Medarević, Đorđe PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4749 AB - 1. INTRODUCTION When it comes to pharmacy, 3D printing has gained immense popularity in recent years due to its revolutionary use in printing drugs tailored to individual patient needs [1,2]. Selective laser sintering (SLS) is an industrial 3D printing technique which uses a powder bed to build up the 3D object thanks to a laser which binds the powder particles together. Advantages of SLS technique include the fact that it is a solvent-free process and offers relatively fast production. Until today, a limited number of studies investigating the production of drug dosage forms using SLS have been reported [2,3]. 2. MATERIALS AND METHODS 2.1. Materials Carvedilol (CRV) was used as a model substance in this study and it was donated by Hemofarm (Vršac, Serbia). The following excipients used to obtain 3D printing tablets: polyvinyl alcohol (PVA, Merck), mannitol (Parteck® M, Merck), Ludipress® (coprocessed excipient consisting of 93% lactose monohydrate, 3.5% crospovidone (Kollidon® CL) and 3.5% povidone K30 (Kollidon® 30), BASF), talc (Merck) and candurin (Candurin® Gold Sheen, Merck). 2.2. Preparation of formulations The compositions of the formulations are shown in Table 1. Table 1. Composition of the formulations Material Formulation 1 Formulation 2 CRV 10% 10% PVA 55% 55% Parteck® M 30% / Ludipress® / 30% Talc 2% 2% Candurin® Gold Sheen 3% 3% Powder for 3D printing was obtained by mixing all the components of the formulation and sifting through a sieve with a diameter of 180 μm. 2.3. 3D printing of oral dosage forms A cylindrical 3D models of the printed tablets (8.00 mm diameter and 2.00 mm thickness) were designed with Autodesk Fusion 360 software version 2.0.8809 (Autodesk Inc, San Rafael, CA, USA), exported as a stereolithography file (.stl) and printed with Sintratec Kit 3D printer (Sintratec AG, Switzerland). The printing parameters were controlled using Sintratec 3D printer software. After a series of variations in temperature and laser speed, the optimal values of these parameters used in the 3D printing process were established and shown in Table 2. Table 2. SLS 3D printing process parameters Surface Temperature ( ◦C) Chamber Temperature ( ◦C) Laser speed (mm/s) Hatch space 80 ºC 70 ºC 60 250 μm 2.4. Mechanical properties of 3D tablets Tablets (n = 10) were weighed on a Sartorius BP 210 D analytical balance (Sartorius, Goettingen, Germany) and measured (diameter and thickness) using a digital caliper (Vogel, Kevelaer, Germany). 2.5. Powder X-ray diffraction analysis (PXRD) PXRD analysis was performed to assess whether the laser induced amorphization of any of the compounds, especially amorphization of poorly soluble CRV. Samples were collected using a Philips PW-1050 (Philips, The Netherlands) diffractometer, operated at 40 kV and 30 mA, using Ni-filtered Cu Kα radiation. 2.6. Dissolution and Drug Release Analysis Dissolution testing was performed under nonsink conditions using mini paddle apparatus (Erweka DT 600, Germany) with a paddle rotation speed of 50 rpm for 8 h, in 100 ml of phosphate buffer (pH 6.8). The amount of dissolved CRV was determined by HPLC method using Dionex Ultimate 3000 (Thermo Scientific, USA) HPLC system. 3. RESULTS AND DISCUSSION 3.1. 3D printing process It was shown that SLS printer was able to fabricate 3D tablets with CRV, as well as that success of the printing process depended on the used printing parameters. 3.2. Mechanical properties of 3D tablets The dimensions of the obtained 3D tablets were in accordance with the defined values of the created 3D models (F1: 8.10 ± 0.08 mm diameter and 2.10 ± 0.13 mm thickness, F2: 8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm thickness). Significant variations in tablet weight between formulations were not observed (m1=0.146 ± 0.04; m2=0.136 ± 0.03). 3.3. Powder X-ray diffraction analysis (PXRD) Figure 1. The X-ray powder diffraction of F1 and F2. 3.4. Dissolution and Drug Release Analysis Figure 2. Dissolution profiles of 3D printing tablets 4. CONCLUSION SLA represents a new chapter in 3D printing of solid oral dosage forms and in individualized therapy in particular. By adjusting the formulation and process parameters, it was possible to produce SLS tablets with coamorphous CRV and PVA as a main polymer. Complete drug release was achieved under non sink conditions after 8 hours in phosphate buffer. The tailoring of drug release might be achieved by varying formulation factors as well as process parameters, although it could be governed by the composition of the whole formulation. PB - Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo C3 - 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts T1 - Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique SP - 210 EP - 211 UR - https://hdl.handle.net/21.15107/rcub_farfar_4749 ER -
@conference{ author = "Pešić, Nikola and Krkobabić, Mirjana and Adamov, Ivana and Ibrić, Svetlana and Ivković, Branka and Medarević, Đorđe", year = "2022", abstract = "1. INTRODUCTION When it comes to pharmacy, 3D printing has gained immense popularity in recent years due to its revolutionary use in printing drugs tailored to individual patient needs [1,2]. Selective laser sintering (SLS) is an industrial 3D printing technique which uses a powder bed to build up the 3D object thanks to a laser which binds the powder particles together. Advantages of SLS technique include the fact that it is a solvent-free process and offers relatively fast production. Until today, a limited number of studies investigating the production of drug dosage forms using SLS have been reported [2,3]. 2. MATERIALS AND METHODS 2.1. Materials Carvedilol (CRV) was used as a model substance in this study and it was donated by Hemofarm (Vršac, Serbia). The following excipients used to obtain 3D printing tablets: polyvinyl alcohol (PVA, Merck), mannitol (Parteck® M, Merck), Ludipress® (coprocessed excipient consisting of 93% lactose monohydrate, 3.5% crospovidone (Kollidon® CL) and 3.5% povidone K30 (Kollidon® 30), BASF), talc (Merck) and candurin (Candurin® Gold Sheen, Merck). 2.2. Preparation of formulations The compositions of the formulations are shown in Table 1. Table 1. Composition of the formulations Material Formulation 1 Formulation 2 CRV 10% 10% PVA 55% 55% Parteck® M 30% / Ludipress® / 30% Talc 2% 2% Candurin® Gold Sheen 3% 3% Powder for 3D printing was obtained by mixing all the components of the formulation and sifting through a sieve with a diameter of 180 μm. 2.3. 3D printing of oral dosage forms A cylindrical 3D models of the printed tablets (8.00 mm diameter and 2.00 mm thickness) were designed with Autodesk Fusion 360 software version 2.0.8809 (Autodesk Inc, San Rafael, CA, USA), exported as a stereolithography file (.stl) and printed with Sintratec Kit 3D printer (Sintratec AG, Switzerland). The printing parameters were controlled using Sintratec 3D printer software. After a series of variations in temperature and laser speed, the optimal values of these parameters used in the 3D printing process were established and shown in Table 2. Table 2. SLS 3D printing process parameters Surface Temperature ( ◦C) Chamber Temperature ( ◦C) Laser speed (mm/s) Hatch space 80 ºC 70 ºC 60 250 μm 2.4. Mechanical properties of 3D tablets Tablets (n = 10) were weighed on a Sartorius BP 210 D analytical balance (Sartorius, Goettingen, Germany) and measured (diameter and thickness) using a digital caliper (Vogel, Kevelaer, Germany). 2.5. Powder X-ray diffraction analysis (PXRD) PXRD analysis was performed to assess whether the laser induced amorphization of any of the compounds, especially amorphization of poorly soluble CRV. Samples were collected using a Philips PW-1050 (Philips, The Netherlands) diffractometer, operated at 40 kV and 30 mA, using Ni-filtered Cu Kα radiation. 2.6. Dissolution and Drug Release Analysis Dissolution testing was performed under nonsink conditions using mini paddle apparatus (Erweka DT 600, Germany) with a paddle rotation speed of 50 rpm for 8 h, in 100 ml of phosphate buffer (pH 6.8). The amount of dissolved CRV was determined by HPLC method using Dionex Ultimate 3000 (Thermo Scientific, USA) HPLC system. 3. RESULTS AND DISCUSSION 3.1. 3D printing process It was shown that SLS printer was able to fabricate 3D tablets with CRV, as well as that success of the printing process depended on the used printing parameters. 3.2. Mechanical properties of 3D tablets The dimensions of the obtained 3D tablets were in accordance with the defined values of the created 3D models (F1: 8.10 ± 0.08 mm diameter and 2.10 ± 0.13 mm thickness, F2: 8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm thickness). Significant variations in tablet weight between formulations were not observed (m1=0.146 ± 0.04; m2=0.136 ± 0.03). 3.3. Powder X-ray diffraction analysis (PXRD) Figure 1. The X-ray powder diffraction of F1 and F2. 3.4. Dissolution and Drug Release Analysis Figure 2. Dissolution profiles of 3D printing tablets 4. CONCLUSION SLA represents a new chapter in 3D printing of solid oral dosage forms and in individualized therapy in particular. By adjusting the formulation and process parameters, it was possible to produce SLS tablets with coamorphous CRV and PVA as a main polymer. Complete drug release was achieved under non sink conditions after 8 hours in phosphate buffer. The tailoring of drug release might be achieved by varying formulation factors as well as process parameters, although it could be governed by the composition of the whole formulation.", publisher = "Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo", journal = "9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts", title = "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique", pages = "210-211", url = "https://hdl.handle.net/21.15107/rcub_farfar_4749" }
Pešić, N., Krkobabić, M., Adamov, I., Ibrić, S., Ivković, B.,& Medarević, Đ.. (2022). Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo., 210-211. https://hdl.handle.net/21.15107/rcub_farfar_4749
Pešić N, Krkobabić M, Adamov I, Ibrić S, Ivković B, Medarević Đ. Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts. 2022;:210-211. https://hdl.handle.net/21.15107/rcub_farfar_4749 .
Pešić, Nikola, Krkobabić, Mirjana, Adamov, Ivana, Ibrić, Svetlana, Ivković, Branka, Medarević, Đorđe, "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique" in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts (2022):210-211, https://hdl.handle.net/21.15107/rcub_farfar_4749 .