Abuse-deterrent features of an extended-release morphine drug product developed using a novel injection-molding technology for oral drug delivery

2017 ◽  
Vol 13 (6) ◽  
pp. 465 ◽  
Author(s):  
Nikolaj Skak, MS ◽  
Torben Elhauge, MSc ◽  
Jeffrey M. Dayno, MD ◽  
Karsten Lindhardt, MSc, PhD, DBE
Keyword(s):  
Injection Molding ◽  
Polymer Matrix ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Pharmaceutical Products ◽  
Oral Drug ◽  
Technology Platform ◽  
Wide Range ◽  
The Guardian

Objective: A novel technology platform (Guardian™ Technology, Egalet Corporation, Wayne, PA) was used to manufacture morphine abuse-deterrent (AD), extended-release (ER), injection-molded tablets (morphine-ADER-IMT; ARYMO® ER [morphine sulfate] ER tablets; Egalet Corporation), a recently approved morphine product with AD labeling. The aim of this article is to highlight how the features of Guardian™ Technology are linked to the ER profile and AD characteristics of morphine-ADER-IMT.Results: The ER profile of morphine-ADER-IMT is attributed to the precise release of morphine from the polymer matrix. The approved dosage strengths of morphine-ADER-IMT are bioequivalent to corresponding dosage strengths of morphine ER (MS Contin®; Purdue Pharma LP, Stamford, CT). Morphine-ADER-IMT was very resistant to physical manipulations intended to reduce particle size, with <10 percent of particles being reduced to <500 μm, regarded by the US Food and Drug Administration as a relevant cutoff for potential insufflation in their generic solid oral AD opioid guidance. Furthermore, morphine was not readily extracted from the polymer matrix of morphine-ADER-IMT in small- or large-volume solvent extraction studies that evaluated the potential for intravenous and oral abuse.Conclusions: The ER profile and AD characteristics of morphine-ADER-IMT are a result of Guardian™ Technology. The combination of the polyethylene oxide matrix and the use of injection molding differentiate morphine-ADER-IMT from other approved AD opioids that deter abuse using physical and chemical barriers. The high degree of flexibility of the Guardian™ Technology enables the development of products that can be tailored to almost any desired release profile; as such, it is a technology platform that may be useful for the development of a wide range of pharmaceutical products.

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

scholarly journals A STUDY ON A NOVEL FORMULATION APPROACH TO DELIVER DOXYCYCLINE THROUGH BUCCAL ROUTE

2019 ◽  
Author(s):  
Tanzeena Afroz ◽  
Md. Jasim Uddin ◽  
Md. Shahidul Islam
Keyword(s):  
Drug Delivery ◽  
Release Rate ◽  
Oral Drug Delivery ◽  
Rapid Onset ◽  
Oral Drug ◽  
Onset Of Action ◽  
Drug Degradation ◽  
Wide Range ◽  
Buccal Films

Recent developments in drug delivery technologies have a great impact on the limitations of traditional oral drug delivery for both the pediatric and geriatric patients. Administration of drug via buccal mucosa is a modern alternative for overcoming low bioavailability, enzymatic inactivation and/or drug degradation in gastrointestinal tract, hence showing rapid onset of action. The aim of the study was to develop doxycycline (antibiotic) loaded buccal films for the treatment of a wide range of systemic and non-systemic bacterial and protozoa infections. The bases of each film were prepared using mucoadhesive polymers, plasticizer, cellulose gums, and instant release film former and penetration enhancer. Optimized films were characterized for weight, width. Length, thickness, surface pH, percentage swelling index, percentage elongation, percentage moisture content, percentage moisture uptake, hydration and in vitro drug release studies. Concentration of different polymers tailored the increase in release rate of doxycycline from the mucoadhesive buccal films. In conclusions, mucoadhesive buccal films can be a substitute route for the delivery of doxycycline as antibacterial or antiprotozoal drug with a faster release rate to reach the site of action.

scholarly journals Preparation of Nifedipine Push-Pull Osmotic Pump Tablets

2020 ◽  
Vol 36 (4) ◽  
Author(s):  
Tran Quang Trung ◽  
Nguyen Thi Dao ◽  
Nguyen Thanh Hai ◽  
Trinh Van Lau
Keyword(s):  
Drug Delivery ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
The United States ◽  
Osmotic Pump ◽  
Oral Drug ◽  
Drug Formulary ◽  
National Drug ◽  
Osmotic Agent ◽  
Formulation Factors

This study aims to investigate the influence of the formulation factors on the drug release kinetics, thereby selecting the compositions of extended-release nifedipine tablet based on the similarity coefficient f2 obtained when compared with Adalat LA tablet. The formulation factors such as: molecular weight of the polyethylene oxide (PEO) and osmotic agent amount in drug layer and push layer, semi permeable membrane thickness (estimated by coating weight gain), orifice size, type of plasticizers and ratios of coating polymer to plasticizer in semipermeable membrane were evaluated. It was found that developed tablets were able to deliver nifedipine in an approximate zero-order manner up to 20 hours and drug release profile of developed tablets was similar to that from Adalat LA tablets. The developed tablet contained: PEO N10, PEO 303 in drug layer and push layer, respectively; percentages of osmotic agent in drug layer and push layer were 10% and 30%, respectively; weight gain of semipermeable coating was 12%; and orifice size was 0.8 mm. Keywords  Nifedipine, GPKD, push-pull osmotic pump, PEO, Tlag. References [1] Vietnamese National Drug Formulary Council, Nifedipine, Vietnamese National Drug Formulary, 2nd edition, Medical Publising House, Hanoi, 2018, pp. 1056-1058 (in Vietnamese).[2] A. Nokhodchi, M.N. Momin, J. Shokri, et al., Factors affecting the release of nifedipine from a swellable elementary osmotic pump, Drug Delivery, 15 (1) (2008) 43-48. https://doi.org/10.1080/10717540701829028[3] R.K. Verma, D.M. Krishna, S. Garg, Formulation aspects in the development of osmotically controlled oral drug delivery systems, Journal of controlled release 79 (1-3) (2002) 7-27. https://doi.org/10.1016/s0168-3659(01)00550-8.[4] The United States Pharmacopeial Convention, Nifedipine Extended-Release Tablets, The United States Pharmacopeia, 41st edition, United Book Press, Baltimore, 2018, pp. 2938 - 2944.[5] V. Malaterre, J. Ogorka, N. Loggia, et al., Approach to design push–pull osmotic pumps, International Journal of Pharmaceutics 376 (1–2) (2009) 56-62. http://dx.doi.org/10.1016/j.ijpharm.2009.04.015.[6] S. Missaghi, P. Patel P, Farrell T. P., et al., Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery, AAPS PharmSciTech 15 (1) (2014) 149-160. http://doi.org/10.1208/s12249-013-0040-4.[7] V. Malaterre, H. Metz, J. Ogorka , et al., Benchtop-magnetic resonance imaging (BT-MRI) characterization of push-pull osmotic controlled release systems, J Control Release 133 (1) (2009) 31-36. http://doi.org/10.1016/j.jconrel.2008.09.007.[8] Z. Zhang, W. Li, S. Nie, et al., Overcome side identification in PPOP by making orifices on both layers, International journal of pharmaceutics 371 (1-2) (2009) 1-7. http://dx.doi.org/10.1016/j.ijpharm.2008.12.006[9] C. Wu, Z. Zhao, Y. Zhao, et al., Preparation of a push–pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core–shell structure, International Journal of Pharmaceutics,475 (1-2) (2014) 298 - 305 . http://dx.doi.org/10.1016/j.ijpharm.2014.08.033.[10] V. Patel, A. Chudasama, M. Nivsarkar, et al., Push-pull osmotic pump for zero order delivery of lithium carbonate: Development and in vitro characterization, Pharmaceutical development and technology, 17 (3) (2012) 375-382. http://doi.org/10.3109/10837450.2010.542577.[11] C.N. Patra, S. Swain, J. Sruti, et al., Osmotic drug delivery systems: Basics and design approaches, Recent Patents on Drug Delivery & Formulation 7(2) (2013) 1 - 12. http://doi.org/10.2174/1872211311307020007.    

scholarly journals FORMULATION AND EVALUATION OF NIFEDIPINE SUSTAINED RELEASE TABLETS BY USING DIFFERENT POLYMERS

2019 ◽  
Vol 8 (5) ◽  
Author(s):  
Shraddha Pawan Pareek ◽  
Sunil Kumawat ◽  
Vijay Sharma ◽  
Devender Sharma ◽  
Devendra Singh Rathore
Keyword(s):  
Drug Delivery ◽  
Sustained Release ◽  
Oral Delivery ◽  
Oral Drug Delivery ◽  
Pharmaceutical Products ◽  
Matrix Tablets ◽  
Oral Drug ◽  
Release Formulation ◽  
Therapeutic Benefits ◽  
Sustained Release Tablets

Oral drug delivery has been known for many years because the most generally utilized route of administration among all the routes that are explored for the general delivery of medication via various pharmaceutical products of different dosage forms.  The reason that the oral route achieved such quality could also be partly attributed to its simple administration moreover because the ancient belief that by oral administration the drug is well absorbed because the food stuffs that area unit eaten daily. In fact the event of a pharmaceutical product for oral delivery, no matter its physical kind involves variable extents of optimization of dose kind characteristics at intervals the inherent constraints of GI physiology.  The rationale for development of a extended release formulation of a drug is to enhance its therapeutic benefits, minimizing its side effects while improving the management of the diseased condition. The aim of the present investigation is to formulate and evaluate matrix tablets of Nifedipine using a mixture of polymers in view to sustain the drug release, reduce frequency of administration and improved patient compliance. In this research paper all evaluation parameter and stability studies also well discussed in well manner. Keyword: Matrix Tablets, Coating, Novel Drug Delivery System, Sustained Release Tablets

scholarly journals A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Maniruzzaman ◽  
Joshua S. Boateng ◽  
Martin J. Snowden ◽  
Dennis Douroumis
Keyword(s):  
Drug Delivery ◽  
Oral Drug Delivery ◽  
Hot Melt Extrusion ◽  
Pharmaceutical Products ◽  
Taste Masking ◽  
Oral Drug ◽  
Melt Extrusion ◽  
Process Technology ◽  
Processing Technologies ◽  
Hot Melt

Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems.

scholarly journals A Review Extended Release Oral Drug Delivery System and Multiparticulate Drug Delivery Systems (MDDS)

2020 ◽  
pp. 84-92
Author(s):  
Swapnil B. Khambat ◽  
Shubham A. Kale.
Keyword(s):  
Drug Delivery ◽  
Dosage Form ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
Oral Dosage ◽  
Oral Drug ◽  
Solid Dosage ◽  
Oral Formulations ◽  
Oral Drug Delivery System ◽  
Oral Dosage Forms

The extended release product will optimize therapeutic effect and safety of a drug at the same time improving the patient convenience and compliance. By incorporating the dose for 24 hrs into one tablet/capsule from which the drug is released slowly. The concept of multiple unit dosage form was initially introduced in the early 1950’s.These forms play a major role in the design of solid dosage form processes because of their unique properties and the flexibility found in their manufacture. These forms can be defined as oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. The release of drug from pellets depends on a variety of factors including the carrier used to form pellets and the amount of drug contained in them. Consequently, pellets provide tremendous opportunities for designing new controlled and extended release oral formulations, thus extending the frontier of future pharmaceutical development. The possible mechanism for drug release includes solution/diffusion through the continuous polymer phase or plasticizer channels, diffusion through aqueous pores and osmotically driven release through aqueous pores. To distinguish between these mechanisms, the release rate was studied as a function of coating thickness, plasticizer content and osmotic pressure in the dissolution medium.

Review on Disease, Dose, Destination and Delivery Aspects of Simvastatin

2020 ◽  
Vol 10 (4) ◽  
pp. 278-287
Author(s):  
Arpna Devi ◽  
Maninder Kumar ◽  
Mohit Kumar ◽  
Uttam K. Mandal
Keyword(s):  
Oral Drug Delivery ◽  
Plga Nanoparticles ◽  
Lipid Lowering ◽  
Oral Drug ◽  
High Permeability ◽  
Wide Range ◽  
Sustained Release Tablets ◽  
Lowering Drug ◽  
Low Solubility ◽  
Oral Drug Delivery Systems

Statins are the choice of drugs for the treatment and management of hypercholesterolaemia because of their established lipid-lowering efficacy and safety profile. Among the various statins, simvastatin is a very popular antihyperlipidemic drug with pleiotropic effects that have a wide range of applications such as antioxidant, anti-inflammatory, antifibrotic effect as well as angiogenic activity. However, poor biopharmaceutical characteristics like low solubility and high permeability make this drug more challenging for formulation scientists in terms its delivery to different targeted areas. Oral drug delivery systems, lipid nanoparticles, PLGA nanoparticles, sustained-release tablets, matrix-type transdermal, co-encapsulating nanostructured lipid carriers are some of the strategies that have been explored to address this issue. This review provides an update regarding the disease, destination, dose and delivery associated with this wonderful lipid-lowering drug molecule.

scholarly journals Prodrug Strategy in Drug Development

2016 ◽  
Vol 62 (3) ◽  
pp. 356-362 ◽  
Author(s):  
Kelemen Hajnal ◽  
Hancu Gabriel ◽  
Rusu Aura ◽  
Varga Erzsébet ◽  
Székely Szentmiklósi Blanka
Keyword(s):  
Drug Development ◽  
Targeted Delivery ◽  
Oral Drug Delivery ◽  
Active Form ◽  
Chemical Properties ◽  
Pharmaceutical Products ◽  
Activation Mechanism ◽  
Oral Drug ◽  
Duration Of Action ◽  
Inactive Form

AbstractProdrugs are chemically modified derivatives introduced in therapy due to their advantageous physico-chemical properties (greater stability, improved solubility, increased permeability), used in inactive form. Biological effect is exerted by the active derivatives formed in organism through chemical transformation (biotransformation). Currently, 10% of pharmaceutical products are used as prodrugs, nearly half of them being converted to active form by hydrolysis, mainly by ester hydrolysis. The use of prodrugs aims to improve the bioavailability of compounds in order to resolve some unfavorable characteristics and to reduce first-pass metabolism. Other objectives are to increase drug absorption, to extend duration of action or to achieve a better tissue/organ selective transport in case of non-oral drug delivery forms. Prodrugs can be characterized by chemical structure, activation mechanism or through the presence of certain functional groups suitable for their preparation. Currently we distinguish in therapy traditional prodrugs prepared by chemical derivatisation, bioprecursors and targeted delivery systems. The present article is a review regarding the introduction and applications of prodrug design in various areas of drug development.

scholarly journals Oral multiunit pellet extended release dosage form: A review

2013 ◽  
Vol 2 (10) ◽  
pp. 177-184 ◽  
Author(s):  
Vishal Sachdeva ◽  
Md. Shoaib Alam ◽  
Ramesh Kumar ◽  
Mahesh Kumar Kataria
Keyword(s):  
Drug Delivery ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
Pharmaceutical Journal ◽  
Oral Drug ◽  
Gastric Residence Time ◽  
Drug Molecules ◽  
Oral Formulations ◽  
Dosing Frequency ◽  
Recent Trends

Oral drug delivery is the most preferred route for the various drug molecules among all other routes of drug delivery, because ease of administration which lead to better patient compliance. So, oral extended release drug delivery system becomes a very promising approach for those drugs that are given orally but having the shorter half-life and high dosing frequency. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving extended release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. The release of drug from pellets depends on a variety of factors including the carrier used to form pellets and the amount of drug contained in them. Consequently, pellets provide tremendous opportunities for designing new controlled and extended release oral formulations, thus extending the frontier of future pharmaceutical development.DOI: http://dx.doi.org/10.3329/icpj.v2i10.16413 International Current Pharmaceutical Journal, September 2013, 2(10): 177-184

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