scholarly journals A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2107
Author(s):  
Bryce W. Barber ◽  
Camille Dumont ◽  
Philippe Caisse ◽  
George P. Simon ◽  
Ben J. Boyd
Keyword(s):  
Drug Release ◽  
Volume Ratio ◽  
Water Soluble ◽  
Dissolution Time ◽  
Lipophilic Drugs ◽  
Solid Lipid ◽  
Area Of Interest ◽  
3D Printed ◽  
Poorly Water Soluble ◽  
Lipid Formulations

3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.

scholarly journals Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1453
Author(s):  
Hellen Windolf ◽  
Rebecca Chamberlain ◽  
Julian Quodbach
Keyword(s):  
Drug Release ◽  
Surface Area ◽  
Volume Ratio ◽  
Dosage Forms ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Alcohol Water ◽  
Wide Range ◽  
3D Printed ◽  
Release Profiles

3D printing offers the advantage of being able to modify dosage form geometry, which can be exploited to modify release characteristics. In this study, we investigated the influence of the surface area to volume ratio (SA/V) to change and predict release profiles of 3D printed dosage forms. Geometries with varying SA/V and dosages were designed and printed, and drug dissolution was investigated. Three drug substances were used: pramipexole, levodopa (both BCS I) and praziquantel (BCS II). Two polymers were chosen as matrix formers: polyvinyl alcohol (water-soluble) and ethylene vinyl acetate (inert). Drug release was characterized using the mean dissolution time (MDT) and established equations that describe complete dissolution curves were applied. Predictions were validated with previously un-printed dosage forms. Based on an identified MDT-SA/V correlation, the MDT can be predicted with a deviation of ≤5 min for a given SA/V. Using correlations of fit parameters and SA/V, RMSEP values of 0.6–2.8% and 1.6–3.4% were obtained for the BCS I formulations and RMSEP values of 1.0–3.8% were obtained for the BCS II formulation, indicating accurate prediction over a wide range of dissolution profiles. With this approach, MDT and release profiles of dosage forms with a given SA/V can be precisely predicted without performing dissolution tests and vice versa, the required SA/V can be predicted for a desired release profile.

NANO-SIZED SOLID DISPERSION OF A POORLY WATER-SOLUBLE DRUG

2012 ◽  
pp. 31-35
Author(s):  
Truong Dinh Thao Tran ◽  
Ha Lien Phuong Tran ◽  
Nghia Khanh Tran ◽  
Van Toi Vo
Keyword(s):  
Drug Release ◽  
Droplet Size ◽  
Solid Dispersion ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
Particle Size Reduction ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Purposes: Aims of this study are dissolution enhancement of a poorly water-soluble drug by nano-sized solid dispersion and investigation of machenism of drug release from the solid dispersion. A drug for osteoporosis treatment was used as the model drug in the study. Methods: melting method was used to prepare the solid dispersion. Drug dissolution rate was investigated at pH 1.2 and pH 6.8. Drug crystallinity was studied using differential scanning calorimetric and powder X-ray diffraction. In addition, droplet size and contact angle of drug were determined to elucidate mechanism of drug release. Results: Drug dissolution from the solid dispersion was significantly increased at pH 1.2 and pH 6.8 as compared to pure drug. Drug crystallinity was changed to partially amorphous. Also dissolution enhancement of drug was due to the improved wettability. The droplet size of drug was in the scale of nano-size when solid dispersion was dispersed in dissolution media. Conclusions: nano-sized solid dispersion in this research was a successful preparation to enhance bioavailability of a poorly water-soluble drug by mechanisms of crystal changes, particle size reduction and increase of wet property.

scholarly journals Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2591
Author(s):  
Thuan Thi Duong ◽  
Antti Isomäki ◽  
Urve Paaver ◽  
Ivo Laidmäe ◽  
Arvo Tõnisoo ◽  
...  
Keyword(s):  
Thin Film ◽  
Drug Release ◽  
Size Distribution ◽  
Water Soluble ◽  
Release Behavior ◽  
Uniform Size ◽  
Ethanol Injection ◽  
Drug Release Behavior ◽  
Poorly Water Soluble

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

scholarly journals Synergistic Effects of Disintegrants on Release of poorly Water soluble drug

2012 ◽  
Vol 1 (3) ◽  
Author(s):  
Md Mofizur Rahman ◽  
Abul Basar Khalpha ◽  
Amit Kumar Chaurasiya ◽  
Mithilesh Kumar Jha ◽  
Md Qamrul Ahsan ◽  
...  
Keyword(s):  
Drug Release ◽  
Synergistic Effects ◽  
Research Work ◽  
Water Soluble ◽  
Dissolution Time ◽  
Release Mechanism ◽  
Sodium Carboxymethylcellulose ◽  
Drug Release Profile ◽  
Fixed Amount ◽  
Sodium Starch Glycolate

We have done research work in lab to find out proper formulation of immediate release tablet by using of various types of disintegrants (crospovidone, sodium starch glycolate and sodium carboxymethylcellulose), in order to examine the effect of mode of absorption of disintegrants on release mechanism from tablets. Acetaminophen, a poor soluble drug was used as a model drug to estimate its release pattern from different formulations. The USP paddle method was selected to perform the dissolution profiles carried out by USP apparatus 2 (paddle) at 50 rpm in 900 ml phosphate buffer pH 5.8. Successive dissolution time, time required for 25%, 50% and 80% of the drug release (T25%, T50%, T80%) was used to evaluate the dissolution results. A One way analysis of variance (ANOVA) was used to recognize the result. Statistically significant differences were found among the drug release profile from all the formulations except mode of addition of crosspovidone. At a fixed amount of disintegrants, extragranular mode of addition seemed to be the best mode of incorporation. The best release was achieved with the sodium carboxymethylcellulose and sodium starch glycolate containing formulations. The T50 and T80 values were analytical of the fact that the drug release was faster from tablet formulations containing carboxymethylcellulose and sodium starch glycolate. The drug release was very much negligible difference by the mode of crospovidone addition. Two formulations found very small T50 and T80 values indicating very much faster release. From the all formulations corresponded extragranular mode of addition could be the best mode of incorporation. The drug release was unaffected by the mode of crospovidone addition. The mode of incorporation of disintegrants suggested enchancing the release of poor soluble drugs. DOI: http://dx.doi.org/10.3329/ijpls.v1i3.12979 International Journal of Pharmaceutical and Life Sciences Vol.1(3) 2012

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.

Encapsulation and drug release of poorly water soluble nifedipine from bio-carriers

2018 ◽  
Vol 481 ◽  
pp. 486-493 ◽  
Author(s):  
Gabrijela Horvat ◽  
Milica Pantić ◽  
Željko Knez ◽  
Zoran Novak
Keyword(s):  
Drug Release ◽  
Water Soluble ◽  
Poorly Water Soluble

scholarly journals Impact of Drug Loading Method on Drug Release from 3D-Printed Tablets Made from Filaments Fabricated by Hot-Melt Extrusion and Impregnation Processes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1607
Author(s):  
Kasitpong Thanawuth ◽  
Lalinthip Sutthapitaksakul ◽  
Srisuda Konthong ◽  
Supakij Suttiruengwong ◽  
Kampanart Huanbutta ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Drug Content ◽  
Loading Method ◽  
Lower Drug ◽  
3D Printed ◽  
Hot Melt

The purpose of this study was to investigate the impact of the drug loading method on drug release from 3D-printed tablets. Filaments comprising a poorly water-soluble model drug, indomethacin (IND), and a polymer, polyvinyl alcohol (PVA), were prepared by hot-melt extrusion (HME) and compared with IND-loaded filaments prepared with an impregnation (IMP) process. The 3D-printed tablets were fabricated using a fused deposition modeling 3D printer. The filaments and 3D printed tablets were evaluated for their physicochemical properties, swelling and matrix erosion behaviors, drug content, and drug release. Physicochemical investigations revealed no drug–excipient interaction or degradation. IND-loaded PVA filaments produced by IMP had a low drug content and a rapid drug release. Filaments produced by HME with a lower drug content released the drug faster than those with a higher drug content. The drug content and drug release of 3D-printed tablets containing IND were similar to those of the filament results. Particularly, drug release was faster in 3D-printed tablets produced with filaments with lower drug content (both by IMP and HME). The drug release of 3D-printed tablets produced from HME filaments with higher drug content was extended to 24 h due to a swelling-erosion process. This study confirmed that the drug loading method has a substantial influence on drug content, which in turn has a significant effect on drug release. The results suggest that increasing the drug content in filaments might delay drug release from 3D-printed tablets, which may be used for developing dosage forms suited for personalized medicine.

scholarly journals EMULSOMES FOR LIPOPHILIC ANTICANCER DRUG DELIVERY: DEVELOPMENT, OPTIMIZATION AND IN VITRO DRUG RELEASE KINETIC STUDY

2021 ◽  
pp. 114-121
Author(s):  
S. DUBEY ◽  
S. P. VYAS
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
Particle Diameter ◽  
Release Profile ◽  
Water Soluble ◽  
Fickian Diffusion ◽  
Release Kinetic ◽  
In Vitro Drug Release ◽  
Solid Lipid

Objective: The objective of the present study was to formulate and characterize paclitaxel (Ptx) loaded sterically stabilized emulsomes to provide non-toxic and biocompatible carriers with high Ptx loading efficiency. Methods: Plain (P-Es) and sterically stabilized emulsomes (SS-Es) were prepared by a modified solvent evaporation method using tristearin as solid lipid and optimized for lipid to (DSPC+CHOL+DSPE-PEG)/ tristearin ratio, lipid/lipid-PEG (DSPC+CHOL/DSPE-PEG) molar ratio, solid lipid concentration, phospholipid concentration, organic to aqueous phase volume and homogenization time based on their effect particle size and entrapment efficiency. Optimized emulsomes were characterized for morphological features, in vitro drug release kinetics and protection from plasma protein. Results: The emulsomes so formed were uniform in size with a mean particle diameter of 275±5.52 and 195±6.4 nm for P-Es and SS-Es respectively. All the formulations showed pH dependent drug release with a slow and sustained release profile. Slower drug release was observed from sterically stabilized emulsomes than the plain emulsomes. The drug release profile followed the Higuchi model with the Fickian diffusion pattern. The Pegylation of emulsomes significantly reduced the in vitro protein absorption. Conclusion: The sterically stabilized emulsome can serve as a novel non-toxic platform with longer circulatory time for the delivery of Paclitaxel and other poorly water-soluble drugs as well.

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