Abstract:
:Low dose micro-tablets with acceptable quality attributes, specifically content uniformity (CU), would not only enhance the dose flexibility in the clinic, but also decrease excipient burden in pediatric population. Considering the CU challenges associated with directly compressed low dose micro-tablets, in this study, high shear wet granulation (HSWG) process was evaluated to manufacture micro-tablets with reduced CU variability. The impact of active pharmaceutical ingredient (API) particle size (D90 - 18-180 µm) and loading (0.67-16.67% w/w) on the critical quality attributes of micro-tablets (1.2 and 1.5 mm) like weight variability, CU, and dissolution were evaluated. Experimental results showed that final blends with flow function coefficient (ffc) ≥ 5.4 or Hausner ratio (HR) ≤ 1.43 facilitated robust compression of micro-tablets. With enhanced weight control, all the batches except the 1.2 mm micro-tablets and 2.0 mm micro-tablets with 0.67% w/w API loading and coarse API particle size (D90 - 180 µm) resulted in CU variability that meets the USP <905> CU acceptance criteria for individual micro-tablets. Apart from the above mentioned 1.2 mm micro-tablets, all the batches meet the USP <905> CU acceptance criteria for composites of 10 or more micro-tablets. Precise delivery of micro-tablets manufactured in the current study would allow dose titration in the increments of 11 mcg. The API particle size and loading impacted the in-vitro dissolution performance of micro-tablets with smaller API particle size and lower loading resulting in faster release profiles. This study provides a framework for developing low dose micro-tablets with acceptable quality attributes using HSWG process for micro-dosing, enhanced dose flexibility, and decreased excipient burden.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Gupta S,Thool P,Meruva S,Li J,Patel J,Agrawal A,Karki S,Bowen W,Mitra Bdoi
10.1016/j.ijpharm.2020.119571subject
Has Abstractpub_date
2020-09-25 00:00:00pages
119571eissn
0378-5173issn
1873-3476pii
S0378-5173(20)30555-Xjournal_volume
587pub_type
杂志文章abstract::A series of diblock copolymers were synthesized by ring-opening polymerization of l- or d-lactide in the presence of monomethoxy poly(ethylene glycol) (mPEG) with molar masses of 2000 and 5000. The aggregation behavior of the resulting water soluble PLA/PEG diblock copolymers in aqueous medium was studied with dynamic...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.04.030
更新日期:2010-07-15 00:00:00
abstract::The development of vaccine delivery systems that will remove or reduce the need for repeated dosing has led to the investigation of sustained release systems. In this context, the duration of antigen release is of great importance as is the requirement for concomitant adjuvant release. In this work, lipid implants con...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.06.052
更新日期:2015-09-30 00:00:00
abstract::Poloxamer-407 (P-407) is a nonionic surfactant that induces atheroma formation in the aortas of C57BL/6 mice with long-term (14 weeks) administration. The objectives of the present study were to determine the mechanism(s) responsible for the induction of hypercholesterolemia as well as to determine whether this animal...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00834-1
更新日期:2001-10-23 00:00:00
abstract::Cyclosporine A (CsA) is a well-known immunosuppressive agent used as rescue therapy in severe steroid-refractory ulcerative colitis (UC). However, toxicity issues associated with CsA when administered in its commercially available formulations have been reported in clinical practice. Since nanotechnology has been prop...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.03.012
更新日期:2016-04-30 00:00:00
abstract::The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.10.064
更新日期:2017-01-10 00:00:00
abstract::In the present study, a novel synthesis technique based on the flow focusing (FF) technology is investigated for the preparation of green fluorescent protein (GFP)-loaded poly(D,L-lactide-co-glycolide) (PLGA) microparticles. To our knowledge, this novel technique has never been applied to the formulation of proteins i...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.07.017
更新日期:2009-10-01 00:00:00
abstract::The effect of 35 newly synthesized O-ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure-activity relationship), an artificial neural network (ANN) was employed. In...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00608-6
更新日期:2001-01-16 00:00:00
abstract::The objective of this study is to evaluate the biodistribution characteristics of liposomes surface-modified with the mixture of polyethylene glycol (PEG) and polyvinyl alcohol (PVA) as a drug carrier for passive targeting of drugs. The liposomes (egg phosphatidylcholine:cholesterol=55:40, molar ratio) modified with b...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.04.004
更新日期:2008-07-09 00:00:00
abstract::Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to investigate the effects of three fatty acid esters on skin permeation. Propylene glycol diperlargonate (DPPG), isopropyl myristate (IPM) and isostearyl isostearate (ISIS) were selected as pharmaceutically relevant solvents...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.02.022
更新日期:2013-04-15 00:00:00
abstract::Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemic...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.11.014
更新日期:2010-02-15 00:00:00
abstract::Metal-based photothermal therapy has been widely used in the biomedicine field and includes gold nanoparticles, silver nanoparticles and copper sulfide nanoparticles. Furthermore, the coordination bonding-based metal nanocomplex is a new generation of photothermal agents for cancer therapy due to its high photothermal...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.06.048
更新日期:2018-10-05 00:00:00
abstract::Dosage forms with fixed dose combinations of drugs is a frequent and advantageous mode of administration, but their production involves a number of technological problems. Numerous interactions in a homogeneous vehicle may be avoided through the use of layered tablets. The mechanical properties of these dosage forms d...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.10.061
更新日期:2015-12-30 00:00:00
abstract::This study explored the transition of lamellar-type liquid crystal (LLC) to biocompatible oil-in-water nanoemulsions able to modify benznidazole (BNZ) release and target the drug to cells infected with the T. cruzi parasite. Three cosolvents (2methylpyrrolidone [NMP], polyethylene glycol [POL], and propylene glycol [P...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.11.041
更新日期:2019-01-30 00:00:00
abstract::Methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) polymeric micelles (PMs) open a promising avenue through which ocular drug delivery with superior efficacy and tolerability can be potentially obtained. Methazolamide (MTZ) is an anti-glaucoma drug exhibiting poor corneal penetration, making it an ideal c...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.06.011
更新日期:2019-07-20 00:00:00
abstract::Topical preparations of capsaicin, the major pungent ingredient of hot pepper, are being used for management of pain and inflammatory disorders. Purpose of this study was to use nanoemulsion as an effective topical drug carrier for in vivo delivery of capsaicin. An oil-in-water nanoemulsion containing capsaicin was pr...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.01.043
更新日期:2019-03-25 00:00:00
abstract::We have evaluated a miniaturized in vitro method, based on the μDISS Profiler™ technique that enables on-line monitoring of drug release from a 21 μl sample with 10 ml of release medium. Four model drugs in eight clinically used formulations, including both solid and non-solid drug delivery systems, were investigated....
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.03.076
更新日期:2015-01-01 00:00:00
abstract::The current first line therapy for oral mucositis pain control is unsatisfactory as it results in only a short duration of modest pain relief. Developing mucoadhesive in situ forming formulations to prolong pain relief is challenging due to their complex physicochemical properties and the unique requirements for oral ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119238
更新日期:2020-04-30 00:00:00
abstract::Distribution of PLGA-microparticles in porcine skin, after its topical application, was studied in vitro using microparticles containing rhodamine as a fluorescent probe. PLGA-microparticles loaded with rhodamine were prepared using a solvent evaporation technique. Skin distribution of fluorescent microparticles was p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00811-0
更新日期:2001-09-11 00:00:00
abstract::Thermosensitive hydrogels are in situ gelling systems composed of hydrophilic homopolymers or block copolymers which remain as solutions at room temperature and form gels after administration into the body. Its application in advanced drug delivery has gained significant attention in recent years. The tunable characte...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.01.030
更新日期:2019-03-25 00:00:00
abstract::The present investigation concerns the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. The importance of the composition optimisation, the technological p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(99)00378-6
更新日期:2000-02-15 00:00:00
abstract::Nanoparticles comprising copolymers of aminoethylcarbamoyl-beta-cyclodextrin (AEC-beta-CD) and ethylene glycol diglycidyl ether (EGDGE) are prepared by an interfacial polyaddition reaction in a miniemulsion system. Polymers are formed in a W/O emulsion containing 0.25-10.0% (w/w) water and 5.0% (w/w) surfactant (MO-3S...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2005.12.015
更新日期:2006-03-27 00:00:00
abstract::An increased number of amorphous formulations of poorly water soluble drugs are being introduced into the market due to their higher transient solubility and thus faster absorption and higher bioavailability. While most amorphous drug products contain a single drug substance, there is a growing trend towards co-formul...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.10.026
更新日期:2015-12-30 00:00:00
abstract::Nanoparticles (NPs) have shown a certain potential to overcome the drawbacks of oral peptide delivery in the gastrointestinal tract such as low peptide stability and permeability. The preparation of insulin loaded NPs was carried out with Eudragit RL or RS dissolved in different non-toxic polyethylene glycol (PEG) der...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.01.017
更新日期:2013-02-25 00:00:00
abstract::The purpose of this study was to construct isotretinoin-loaded SLN (IT-SLN) formulation with skin targeting for topical delivery of isotretinoin. PRECIROL ATO 5 was selected as the lipid of SLN. Tween 80 and soybean lecithin were used as the surfactants to stabilize SLN. The hot homogenization method was performed to ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.08.007
更新日期:2007-01-10 00:00:00
abstract::The aim of this study was to evaluate the transdermal permeation enhancement of N-trimethyl chitosan (TMC) with different degrees of quaternization (DQ). TMCs with DQ of 40 and 60% (TMC40 and TMC60) were synthesized and characterized by (1)H NMR. Testosterone (TS) used as an effective drug, four different gels were pr...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2007.12.050
更新日期:2008-05-22 00:00:00
abstract::The particle size of peptide DNA condensates were studied after freeze-drying and rehydration as a function of sugar excipient, concentration, pH, DNA concentration, and peptide condensing agent. In the absence of an excipient, freeze-dried 50 microg/ml AlkCWK(18) (iodoacetic acid alkylated Cys-Typ-Lys(18)) DNA conden...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00435-x
更新日期:2000-08-10 00:00:00
abstract::A relatively high molecular weight of 4-arm star PELA was obtained by ring-opening polymerization of l-lactic acid O-carboxyanhydride with 4-arm-PEG in the presence of DMAP as an initiator. The results via(1)H NMR and (13)C NMR show that the end of the star PELA chain is a hydroxyl group and the central core is a PEG ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.05.074
更新日期:2015-08-01 00:00:00
abstract::The aim of the current study is to explore the potential of PEG-30-dipolyhydroxystearate (Cithrol(®) DPHS) and Soluplus(®) as ingredients in novel semisolid self-nanoemulsifying drug delivery systems (SNEDDS). Semisolid SNEDDS consisting of Cithrol(®) DPHS, Capmul(®) MCM and Kolliphor(®) HS 15 were successfully prepar...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2014.10.063
更新日期:2014-12-30 00:00:00
abstract::Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as a new drug nanocarrier system for improving bioavailability for both hydrophilic and hydrophobic drugs. In this study, self-assembled LCNPs based on soy phosphatidyl choline and glycerol dioleate, which was known possessing low tox...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.12.058
更新日期:2012-03-15 00:00:00
abstract::In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids re...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.10.012
更新日期:2012-12-15 00:00:00