Gastroretentive Microspheres: An Innovative Approach for Prolonging Gastric Residence

Gastro-retentive drug delivery systems (GRDDS) like gastro-retentive microspheres have gained immense popularity in the field of oral drug delivery. It is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. Different innovative approaches like magnetic field assisted gastro-retention, swelling systems, mucoadhesion techniques, floating systems with or without effervescence are being applied to fabricate gastroretentive microspheres. Apart from in-vitro characterization, successful gastro-retentive microspheres development demands well designed in-vivo study to establish enhanced gastro-retention and prolonged drug release. Gama scintigraphy and MRI are popular techniques to evaluate in-vivo gastric residence time. However, checking of their overall in-vivo efficacy still remains a major challenge for this kind of dosage form, especially in small animals like mice or rat. Reported in-vivo studies with beagle dogs, rabbits, and human subjects are only a handful in spite of a large number of encouraging in-vitro results. In spite of the many advantages, high subject variations in gastrointestinal physiological condition, effect of food, and variable rate of gastric emptying time are the challenges that limit the availability of gastro-retentive microspheres in the market.

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In vitro and in vivo studies of enzyme-digestible hydrogels for oral drug delivery

Journal of Controlled Release ◽

10.1016/0168-3659(92)90071-x ◽

1992 ◽

Vol 19 (1-3) ◽

pp. 131-144 ◽

Cited By ~ 31

Author(s):

Waleed S.W. Shalaby ◽

William E. Blevins ◽

Kinam Park

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

In Vivo Studies ◽

Oral Drug

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Bioadhesive Mannosylated Nanoparticles for Oral Drug Delivery

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.445 ◽

2006 ◽

Vol 6 (9) ◽

pp. 3203-3209 ◽

Cited By ~ 46

Author(s):

Hesham H. Salman ◽

Carlos Gamazo ◽

Miguel A. Campanero ◽

Juan M. Irache

Keyword(s):

Drug Delivery ◽

Oral Delivery ◽

Oral Drug Delivery ◽

Normal Mucosa ◽

Oral Drug ◽

Con A ◽

Distribution Profile ◽

The Given

The aim of this work was to design mannosylated Gantrez® AN nanoparticles (M-NP) and to describe their gut bioadhesive properties in order to develop a promising carrier for future applications in oral drug delivery. For that purpose, the process of the nanoparticles coating with mannosamine was optimized by the incubation of Gantrez® AN nanoparticles with different volumes of mannosamine aqueous solutions at different times. Then, the nanoparticles were characterized by measuring the size, zeta potential, mannosamine content, and concanavalin A (Con A) binding. Furthermore, in vivo quantitative bioadhesion study and kinetic analysis of the bioadhesion curves were performed after oral administration to rats of fluorescently labelled nanoparticles. The selected mannosylated nanoparticles (M-NP1 and M-NP10) were of homogenous sizes (about 300 and 200 nm), negatively charged and successfully coated with 36 and 18 μg mannosamine/mg NP, respectively. In vitro agglutination assay using Con A confirmed the successful coating of nanoparticles with mannosamine. The gut distribution profile of M-NP1 indicated a stronger bioadhesive capacity than M-NP10 and non-mannosylated ones, 1 h post-administration. Interestingly, M-NP1 showed an important ileum tropism where around 20% of the given dose remained adhered. Besides, the kinetic parameters of the bioadhesion profile of M-NP1 indicated their higher bioadhesive capacity with Qmax and AUCadh about 2-times higher than control ones. Moreover, fluorescence microscopy corroborated the stronger interactions of M-NP1 with the normal mucosa and demonstrated a strong uptake of these carriers by Peyer's patches. In conclusion, we propose that mannosylated nanoparticles could be a promising non-live vector for oral delivery strategies.

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In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms

Pharmaceutics ◽

10.3390/pharmaceutics11080416 ◽

2019 ◽

Vol 11 (8) ◽

pp. 416 ◽

Cited By ~ 3

Author(s):

Schneider ◽

Koziolek ◽

Weitschies

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Oral Drug Delivery ◽

Test Methods ◽

Delivery Systems ◽

Oral Drug ◽

Gastrointestinal Physiology ◽

In Vivo Test

More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems.

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Stearic Acid-g-chitosan Polymeric Micelle for Oral Drug Delivery: In Vitro Transport and in Vivo Absorption

Molecular Pharmaceutics ◽

10.1021/mp100289v ◽

2010 ◽

Vol 8 (1) ◽

pp. 225-238 ◽

Cited By ~ 81

Author(s):

Hong Yuan ◽

Lin-Juan Lu ◽

Yong-Zhong Du ◽

Fu-Qiang Hu

Keyword(s):

Drug Delivery ◽

Stearic Acid ◽

Oral Drug Delivery ◽

Polymeric Micelle ◽

Oral Drug ◽

In Vivo Absorption

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Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics12121194 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1194

Author(s):

Aristote B. Buya ◽

Ana Beloqui ◽

Patrick B. Memvanga ◽

Véronique Préat

Keyword(s):

Drug Delivery ◽

Patient Compliance ◽

Oral Delivery ◽

Drug Delivery Systems ◽

Water Solubility ◽

Oral Drug Delivery ◽

Delivery Systems ◽

Oral Drug ◽

Statistical Design Of Experiments

Approximately one third of newly discovered drug molecules show insufficient water solubility and therefore low oral bio-availability. Self-nano-emulsifying drug-delivery systems (SNEDDSs) are one of the emerging strategies developed to tackle the issues associated with their oral delivery. SNEDDSs are composed of an oil phase, surfactant, and cosurfactant or cosolvent. SNEDDSs characteristics, their ability to dissolve a drug, and in vivo considerations are determinant factors in the choice of SNEDDSs excipients. A SNEDDS formulation can be optimized through phase diagram approach or statistical design of experiments. The characterization of SNEDDSs includes multiple orthogonal methods required to fully control SNEDDS manufacture, stability, and biological fate. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The transformation of liquid SNEDDSs into solid dosage forms has been shown to increase the stability and patient compliance. Supersaturated, mucus-permeating, and targeted SNEDDSs can be developed to increase efficacy and patient compliance. Self-emulsification approach has been successful in oral drug delivery. The present review gives an insight of SNEDDSs for the oral administration of both lipophilic and hydrophilic compounds from the experimental bench to marketed products.

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Design and in vivo Evaluation of Gastro-retentive Floating Capsules of Amlodipine Besylate in Healthy Human Volunteers

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2017.10.6.3 ◽

2017 ◽

Vol 10 (6) ◽

pp. 3891-3899

Author(s):

Bhikshapathi D. V. R. N. ◽

Chenna Madipalli Shalina ◽

Vishnu Pulavarthy ◽

Viswaja Medipally

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Sustained Release ◽

In Vivo Studies ◽

Amlodipine Besylate ◽

In Vivo Evaluation ◽

Healthy Human ◽

Gastro Retentive

The aim of this study was to explore the application of Gelucire 43/01 for the design of sustained release gastro retentive drug delivery system of Amlodipine besylate. Gelucire 43/01 has been used in floating sustained release formulations to prolong gastric residence time and increase its bioavailability. Gelucire 43/01 in combination with HPMC and Polyox was used as a release retarding polymer. HPMC of various viscosity grades HPMC K4M, HPMC K15M and HPMC K100M in combination of Gelucire were tested to obtain optimal total floating time as well as controlled drug release for prolonged period. Melt granulation technique has been used to prepare gastro retentive Amlodipine besylate formulations. All the formulations were evaluated in vitro for their floating ability and drug release. The floating times of all tablet formulations were greater than 12h. HPMC K4M in combination with Gelucire as polymeric matrix enhanced the drug release due to addition of hydrophilic polymer facilitated the swelling and erosion of the tablets. Incorporation of low viscosity polymer HPMC K100 M resulted in optimal floating as well as drug release for longer time. In vivo studies of optimized formulation show floating ability for 6 h in stomach. The results indicate that Gelucire 43/01 in combination with dissolution enhancers HPMC increase the permeability of the wax matrix, which provides improved dissolution thereby bioavailability of Amlodipine besylate and can be considered as a carrier for the development of sustained release floating drug delivery systems.

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Determination of the in vitro and in vivo oral drug delivery capabilities of complexation hydrogels

10.17918/etd-1305 ◽

2021 ◽

Author(s):

Eric D. Perakslis

Keyword(s):

Drug Delivery ◽

Oral Drug Delivery ◽

Oral Drug

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Design of a Soft, Self-Uncoiling Stent for Extended Retention of Drug Delivery in the Small Intestine

2021 Design of Medical Devices Conference ◽

10.1115/dmd2021-1063 ◽

2020 ◽

Author(s):

Sunandita Sarker ◽

Ryan Jones ◽

Gabriel Chow ◽

Benjamin Terry

Keyword(s):

Drug Delivery ◽

Small Intestine ◽

Oral Drug Delivery ◽

Ileocecal Valve ◽

Drug Carriers ◽

Oral Formulation ◽

In Vivo Studies ◽

Oral Drug ◽

Biological Drugs

Abstract Despite being the preferred route of drug administration, the oral formulation of biological drugs is limited due to its intrinsic instability, low permeability, and physical, chemical and immunological barriers. Various innovative swallowable technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities. The current work presents a novel soft stent platform that can facilitate contact between the small intestine tissue and drug carriers to enhance drug absorption and increase residence time. This study aims to prove the concept of this novel platform and determine if the soft stent will retain orally to the ileocecal valve longer than a capsule-shaped bolus. Benchtop studies on an intestinal simulator showed successful retention of the soft stent compared to a control capsule. In vivo studies in pig models also showed that the soft stent was retained longer than the control capsule. Overall, this study shows promise that this novel platform could be used for oral drug delivery of biologics.

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