3D printing of extended-release tablets of theophylline using hydroxypropyl methylcellulose (HPMC) hydrogels

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

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LINAGLIPTIN AND GLICLAZIDE DI-LOADED EXTENDED-RELEASE NANOPARTICLES: FORMULATION AND EVALUATION

Wiadomości Lekarskie ◽

10.36740/wlek202109212 ◽

2021 ◽

Vol 74 (9) ◽

pp. 2315-2322

Author(s):

Firas Aziz Rahi ◽

Muath Sheet Mohammed Ameen ◽

Mohammed Shamil Fayyadh

Keyword(s):

Particle Size ◽

Xanthan Gum ◽

Extended Release ◽

Hydroxypropyl Methylcellulose ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Hplc Method ◽

Electronic Microscopy ◽

Vitro Release

The aim: This work aimed to formulate gliclazide and linagliptin extended-release nanoparticles. Materials and methods: A HPLC method was developed and validated to determine gliclazide and linagliptin at the same time without interference. The nanoparticles were prepared by emulsion solvent evaporation using two polymers, namely hydroxypropyl methylcellulose (HPMC) 4000 cps and xanthan gum. Results: Nanoparticles prepared were characterized for drug contents, production yield and entrapment efficiency, zeta potential, particle size, morphology by transmission electronic microscopy (TEM) and in-vitro release rate. The formulae GLH1, GLX1 and GHX1 showed release of linagliptin more than 75% after 8 hrs. While the only formula among the three (GHX1) showed release of gliclazide more than 80% after 8 h. So, the formula GHX1 showed acceptable release of more than 80% of both gliclazide and linagliptin after 8 h. Conclusions: The formula GHX1 which containing (0.5:1 xanthan gum: drugs) was the best nanoparticles formula which released more than 80% of both drugs after 8 h and could achieve good extended release over 24 h.

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Effects of Manufacturing Process Variables on In Vitro Dissolution Characteristics of Extended-Release Tablets Formulated with Hydroxypropyl Methylcellulose

Drug Development and Industrial Pharmacy ◽

10.1081/ddc-120016686 ◽

2003 ◽

Vol 29 (1) ◽

pp. 79-88 ◽

Cited By ~ 22

Author(s):

Ye Huang ◽

Kavita H. Khanvilkar ◽

Angela D. Moore ◽

Marquetta Hilliard-Lott

Keyword(s):

Manufacturing Process ◽

Extended Release ◽

Hydroxypropyl Methylcellulose ◽

In Vitro Dissolution ◽

Process Variables

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Fast, Spectroscopy-Based Prediction of In Vitro Dissolution Profile of Extended Release Tablets Using Artificial Neural Networks

Pharmaceutics ◽

10.3390/pharmaceutics11080400 ◽

2019 ◽

Vol 11 (8) ◽

pp. 400 ◽

Cited By ~ 3

Author(s):

Galata ◽

Farkas ◽

Könyves ◽

Mészáros ◽

Szabó ◽

...

Keyword(s):

Raman Spectra ◽

Extended Release ◽

Near Infrared ◽

Hydroxypropyl Methylcellulose ◽

In Vitro Dissolution ◽

Dissolution Profile ◽

Ann Model ◽

Compression Force ◽

Ann Models ◽

Artificial Neural

The pharmaceutical industry has never seen such a vast development in process analytical methods as in the last decade. The application of near-infrared (NIR) and Raman spectroscopy in monitoring production lines has also become widespread. This work aims to utilize the large amount of information collected by these methods by building an artificial neural network (ANN) model that can predict the dissolution profile of the scanned tablets. An extended release formulation containing drotaverine (DR) as a model drug was developed and tablets were produced with 37 different settings, with the variables being the DR content, the hydroxypropyl methylcellulose (HPMC) content and compression force. NIR and Raman spectra of the tablets were recorded in both the transmission and reflection method. The spectra were used to build a partial least squares prediction model for the DR and HPMC content. The ANN model used these predicted values, along with the measured compression force, as input data. It was found that models based on both NIR and Raman spectra were capable of predicting the dissolution profile of the test tablets within the acceptance limit of the f2 difference factor. The performance of these ANN models was compared to PLS models using the same data as input, and the prediction of the ANN models was found to be more accurate. The proposed method accomplishes the prediction of the dissolution profile of extended release tablets using either NIR or Raman spectra.

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FORMULATION A CIPROFLOXACIN HYDROCHLORIDE EXTENDED-RELEASE TABLET WITH COMBINATION OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) K100M AND HYDROXYPROPYL METHYLCELLULOSE (HPMC) K4M BY DIRECT COMPRESSION METHOD

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i1.35522 ◽

2019 ◽

pp. 25-30

Author(s):

RESMI MUSTARICHIE ◽

DOLIH GOZALI ◽

YEDI HERDIANA

Keyword(s):

Statistical Analysis ◽

Extended Release ◽

Hydroxypropyl Methylcellulose ◽

Hardness Test ◽

Dissolution Test ◽

Test Results ◽

Ciprofloxacin Hydrochloride ◽

Uniformity Test ◽

Size Uniformity ◽

Release Tablet

Objective: Ciprofloxacin hydrochloride tablets which are not extended-release will produce non-constant drug levels in the blood. This study aimed to overcome this problem by making ciprofloxacin hydrochloride extended-release tablets with a combination of hydroxypropyl methylcellulose (HPMC) K100M and hydroxypropyl methylcellulose (HPMC) K4M by a direct compression method. Methods: The method in this study consisted of preformulation, formula design, manufacture of ciprofloxacin hydrochloride tablets, tablet print mass testing, IPC (In-Process Control) slow-release tablet mass print, IPC (In-Process Control) quality of slow-release tablet preparation, dissolution test, and statistical analysis. Preformulation was carried out aiming to determine the physical and chemical properties of active-excipient substances based on a certificate of analysis. This was done using a Fourier Transform Infrared (FT-IR) and UV-Vis spectrophotometer. Five kinds of ciprofloxacin hydrochloride tablet formulations were made using the direct pressing method with variations in the concentration of HPMC K100M and HPMC K4M. The ratio of percentage of HPMC K100M and HPMC K4M were F1 0,5%: 1%, F2 1%: 0,5%, F3 0,75%: 0,75%, F4 1%: 0%, F5 0%: 3%. Evaluation of tablet preparations (IPC control) included weight uniformity test, size uniformity test, hardness test, and friability test. The dissolution test was carried out for 2 h by hydrochloride acid 0,1 N pH 1.2 as (pH of gastric acid). Statistical analysis using Perfect Block Random Design (PBRD) method and further testing using the Newman-Keuls test was applied for the data obtained. Results: The test results with FTIR showed that ciprofloxacin hydrochloride used compared to ciprofloxacin hydrochloride BPFI is equivalent and has a purity index of 0.992739. Determination of the level of the active ingredient ciprofloxacin hydrochloride was carried out by measuring the absorbance of a 5 ppm sample solution at a wavelength of 276 nm. The percentage of absorbance of the solution is then calculated and the result obtained is 98.87%. The range of levels that have been set is 98%-102%. These test results were under those listed on the certificate of analysis. The results of the IPC test in the form of weight uniformity test, size uniformity test, hardness test, friability test, and uniformity of ciprofloxacin hydrochloride levels in the preparation, showed all data obtained fulfilling the requirements set by USP 36 convention (2013). The result from dissolution tablet test on 30, 60, and 120 min showed the release of active substance on F1 56.00 %, 67.76 %, and 87.57 %. F2 were 53.42 %, 65.16 %, and 91.44 %. F3 were 59.18 %, 72.15 %, and 91.20 %. F4 were 50.51 %, 70.70 %, and 95.29 %. F5 were 53.75 %, 69.55 %, and 92.05 %. Statistical analysis was applied for the data obtained. Dissolution results illustrated the level of active substances dissolved in the dissolution medium for 2 h or in other words the dissolution test results indicated the number of active substances from tablets that were released and enter the digestive tract and came in contact with body fluids. Conclusion: The dissolution test results as a basis of extended-release tablets showed all of the formulae met dissolution requirements of the United States Pharmacopeia (USP) 36 convention.

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3D Printing Geometric Scaffold Design Variation of Injectable Bone Substitutes (IBS) Pa

Indonesian Applied Physics Letters ◽

10.20473/iapl.v1i2.23447 ◽

2020 ◽

Vol 1 (2) ◽

pp. 55

Author(s):

Dyah Hikmawati ◽

Sarda Nugraheni ◽

Aminatun Aminatun

Keyword(s):

Drug Delivery ◽

Compressive Strength ◽

3D Printing ◽

Hydroxypropyl Methylcellulose ◽

Bone Substitutes ◽

Fused Deposition Modelling ◽

Scaffold Design ◽

Technology Application ◽

Fused Deposition ◽

Before And After

3D printing technology application in tissue engineering could be provided by designing geometrical scaffold architecture which also functionates as drug delivery. For drug delivery scaffold on bone tuberculosis, the cell pore of the geometric design was filled with Injectable Bone Substitutes (IBS) which had streptomycin as anti-tuberculosis. In this study, scaffolds were synthesized in three cells geometric filled by Injectable Bone Substitutes (IBS), Hexahedron, Truccated Hexahedron, and Rhombicuboctahedron, which had 2.5 mm x 2.5 mm x 2.5 mm size dimension and 0.8 mm strut. The final design was printed in 3D with polylactic acid (PLA) filament using the FDM process (Fused Deposition Modelling). The composition of IBS paste was a mixture of hydroxyapatite (HA) and gelatine (GEL) 20% w/v with a ratio of 60:40, streptomycin 10 wt% and hydroxypropyl methylcellulose (HPMC) 4% w/v. It was then characterized using Fourier-transform infrared spectroscopy (FTIR). Scaffold–paste characterization was included pore size test of 3D printing result before and after injected using Scanning Electron Microscope SEM, porosity test, and compressive strength test. The result showed that the pore of scaffold design was 1379 µm and after injected with IBS paste, the pore leaving 231.04 µm of size. The scaffold with IBS paste porosity test showed ranges between 40,78-70,04% while the compressive strength of before and after injected ranges between 1,110-634 MPa and 2,217-6,971 MPa respectively. From the test results, the scaffold 3D printing with IBS paste in this study had suitable physical characteristics to be applicated on cancellous bones which were infected by tuberculosis.

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Fabrication of Muco-Adhesive Oral Films by the 3D Printing of Hydroxypropyl Methylcellulose-Based Catechin-Loaded Formulations

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.b19-00481 ◽

2019 ◽

Vol 42 (11) ◽

pp. 1898-1905 ◽

Cited By ~ 4

Author(s):

Tatsuaki Tagami ◽

Natsumi Yoshimura ◽

Eiichi Goto ◽

Takehiro Noda ◽

Tetsuya Ozeki

Keyword(s):

3D Printing ◽

Hydroxypropyl Methylcellulose ◽

Oral Films

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A Feasibility Study on HPMC-Improved Sulphoaluminate Cement for 3D Printing

Materials ◽

10.3390/ma11122415 ◽

2018 ◽

Vol 11 (12) ◽

pp. 2415 ◽

Cited By ~ 8

Author(s):

Zhu Ding ◽

Xiaodong Wang ◽

Jay Sanjayan ◽

Patrick Zou ◽

Zhi-Kun Ding

Keyword(s):

Compressive Strength ◽

3D Printing ◽

Feasibility Study ◽

Setting Time ◽

Hydroxypropyl Methylcellulose ◽

Hydration Heat ◽

Heat Setting ◽

Sulphoaluminate Cement ◽

Final Setting Time ◽

Experimental Parameters

A novel 3D printing material based on hydroxypropyl methylcellulose (HPMC)—improved sulphoaluminate cement (SAC) for rapid 3D construction printing application is reported. The hydration heat, setting time, fluidity of paste and mortar, shape retainability, and compressive strength of extruded SAC mortar were investigated. HPMC dosage, water-to-cement (W/C) ratio, and sand-to-cement (S/C) ratio were studied as the experimental parameters. Hydration heat results reveal HPMC could delay the hydration of SAC. The initial and final setting time measured using Vicat needle would be shortened in the case of W/C ratio of 0.3 and 0.35 with HPMC dosage from 0.5% to 1.5%, W/C ratio of 0.40 with HPMC dosage of 0.5%, 0.75%, and 1.5%, and W/C ratio of 0.45 with HPMC dosage of 0.45, or be extended in the case of W/C ratio of 0.4 with HPMC dosage of 1.0% and W/C ratio of 0.45 with HPMC dosage from 0.75% to 1.5%. Fluidity measurement shows HPMC significantly improves the shape retainability. Furthermore, the addition of HPMC remarkably increased the compressive strength of extruded mortar. The results showed that HPMC could be used to prepare 3D printing SAC having satisfactory shape retainability, setting time and compressive strength.

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