In polymer degradation and durability studies, as well as predicting shelf-life for medical devic... more In polymer degradation and durability studies, as well as predicting shelf-life for medical devices, one is confronted with the need for accurate prediction and difficulties of long term real-time evaluation. Various ways to accelerate the degradation process have met with mixed success. However, recently, in our own studies, a ‘master curve’ like behavior was found to be valid for polypropylene samples studied. Evidently, for samples obeying the master curve, very few data points at high temperatures can be scaled to obtain reasonably accurate estimates on long term durability. Nevertheless, in a reference medium density polyethylene (MDPE) film material, the high temperature oxidative induction time data appear to diverge when run under air atmosphere compared with oxygen environments. In this article, we will present data on many of the polymer systems studied with an emphasis on extrapolation schemes for high temperature accelerated data to lower temperature very long-term durability. In this context, polymer and antioxidant reactivity toward oxygen, morphology, and mechanical property dependence on extent of degradation all need to be considered. And the potential and limitations of this approach will be discussed.
For medical¯uid delivery applications, clear materials with both low modulus and high temperature... more For medical¯uid delivery applications, clear materials with both low modulus and high temperature resistance are highly sought after. Many of the currently available materials are either optically opaque, or far too expensive to be suited for the majority of applications. The recently available stereoblock homo-polypropylene polymers, where atactic and isotactic sequences are placed on the main-chain, present an attractive opportunity. We have examined some of these commercial as well as experimental polymers by thermal analysis, rheology and mechanical analysis for their potential suitability in medical applications. #
A polyethylene ®lm with phenolic antioxidant and phosphite synergist, has been proposed to be a s... more A polyethylene ®lm with phenolic antioxidant and phosphite synergist, has been proposed to be a standard reference material for the oxidative induction time measurement by DSC (differential scanning calorimetry) [R.L. Blaine, A proposed reference material for oxidative induction time by differential scanning calorimetry, in: A.]. We have examined the oxidative stability of this material over diverse conditions. These include oxidative induction time in air, over broad temperatures; induction time in pressurized oxygen in a pressure DSC, circulating oven, and samples subjected to different doses of ionizing radiation. It appears that when the lifetime is presented in the Arrhenius form, a progressively diminishing activation energies toward room temperature was observed. After combining experimental OIT (oxidative induction time) data of up to about 8 years, a conservative estimate of durability of about 30 years was obtained. # 2000 Published by Elsevier Science B.V.
Metallocene polymerized ultralow density polyethylenes (ULDPE) were found to be effective impact ... more Metallocene polymerized ultralow density polyethylenes (ULDPE) were found to be effective impact modi®ers for rigid matrices such as polypropylene (PP). This is mainly due to the very high level of comonomer incorporation with homogeneous short chain branching distributions (SCBD) brought about by the single site metallocene catalysts. However, a very heterogeneous Ziegler Natta copolymer of 0.88 speci®c gravity was found to be surprisingly effective in impact modi®cation ef®ciency.
Journal of Biomaterials Science-polymer Edition, 1993
Controlled release systems of theophylline, proxyphylline and oxprenolol.HCl exhibiting modulated... more Controlled release systems of theophylline, proxyphylline and oxprenolol.HCl exhibiting modulated drug delivery were prepared by using pH-sensitive anionic copolymers of 2-hydroxyethyl methacrylate with acrylic acid or methacrylic acid. Drug release studies were carried out in simulated biological fluids. The initial drug release rates and the drug release mechanisms were dependent upon the pH and ionic strength of the buffer solution as well as its salt composition. Initial drug diffusion coefficients in these swelling-controlled release systems were calculated from the release curves; they were of the order of 10(-7) cm2/s and were dependent upon the degree of swelling. The drug release mechanism was non-Fickian in all the dissolution media studied. Lowest release rates were observed for drug release from nonionized polymer networks in agreement with the relationship between ionization, swelling and drug release.
There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs... more There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved bioavailability, nanoparticles can also provide targeting capabilities when injected intravenously. The latter property has led to increased research and development activities for intravenous suspensions. The first intravenously administered nanoparticulate product, Abraxane (a reformulation of paclitaxel), was approved by the FDA in 2006. Additional clinical trials have been conducted or are ongoing for multiple other indications such as oncology, infective diseases, and restenosis. This article reviews various challenges associated with developing intravenous nanosuspension dosage forms. In addition, various formulation considerations specific to intravenous nanosuspensions as well as reported findings from various clinical studies have been discussed.
In order to further our understanding of polymer durability, the degradation kinetics of a series... more In order to further our understanding of polymer durability, the degradation kinetics of a series of polymers was studied. The Arrhenius activation energy was used as the parameter to follow the rate dependence as a function of temperature. For most systems, it was evident that the apparent activation energies increase monotonically with temperature. This ®nding explains the frequent observation that kinetic parameters obtained at high temperatures often lead to grossly optimistic estimates of shelf life at ambient conditions. The activation energies of polypropylene from the surface embrittlement processes were also found to have a striking similarity to the thermal processes, with nearly identical activation energies at the same temperature. A good understanding of this observation could lead to broader applications and further the understanding of polymer degradation. # 2001 Published by Elsevier Science B.V.
Since the development of the oxidative induction time (OIT) test by former Bell Telephone Laborat... more Since the development of the oxidative induction time (OIT) test by former Bell Telephone Laboratories researchers, there have been many studies to broaden its applicability to polymers beyond the original polyole®ns. The basic premise in OIT studies is that a detectable oxidation onset is based on the differential reactivity between the polymer matrix and free radical scavenging antioxidants like hindered phenols. This situation does not exist in depolymerizing systems such as polymethylmethacrylates (PMMA), so many researchers concluded that a correlation did not exist for these systems. We will report on the observation of a clear cut, Arrhenius-like oxidative induction time behavior in a toughened PMMA system with high pressure DSC. The relationship between the observed OIT at elevated temperatures and high oxygen pressures with lower temperature oven aging studies will be presented. #
In polymer degradation and durability studies, as well as predicting shelf-life for medical devic... more In polymer degradation and durability studies, as well as predicting shelf-life for medical devices, one is confronted with the need for accurate prediction and difficulties of long term real-time evaluation. Various ways to accelerate the degradation process have met with mixed success. However, recently, in our own studies, a ‘master curve’ like behavior was found to be valid for polypropylene samples studied. Evidently, for samples obeying the master curve, very few data points at high temperatures can be scaled to obtain reasonably accurate estimates on long term durability. Nevertheless, in a reference medium density polyethylene (MDPE) film material, the high temperature oxidative induction time data appear to diverge when run under air atmosphere compared with oxygen environments. In this article, we will present data on many of the polymer systems studied with an emphasis on extrapolation schemes for high temperature accelerated data to lower temperature very long-term durability. In this context, polymer and antioxidant reactivity toward oxygen, morphology, and mechanical property dependence on extent of degradation all need to be considered. And the potential and limitations of this approach will be discussed.
For medical¯uid delivery applications, clear materials with both low modulus and high temperature... more For medical¯uid delivery applications, clear materials with both low modulus and high temperature resistance are highly sought after. Many of the currently available materials are either optically opaque, or far too expensive to be suited for the majority of applications. The recently available stereoblock homo-polypropylene polymers, where atactic and isotactic sequences are placed on the main-chain, present an attractive opportunity. We have examined some of these commercial as well as experimental polymers by thermal analysis, rheology and mechanical analysis for their potential suitability in medical applications. #
A polyethylene ®lm with phenolic antioxidant and phosphite synergist, has been proposed to be a s... more A polyethylene ®lm with phenolic antioxidant and phosphite synergist, has been proposed to be a standard reference material for the oxidative induction time measurement by DSC (differential scanning calorimetry) [R.L. Blaine, A proposed reference material for oxidative induction time by differential scanning calorimetry, in: A.]. We have examined the oxidative stability of this material over diverse conditions. These include oxidative induction time in air, over broad temperatures; induction time in pressurized oxygen in a pressure DSC, circulating oven, and samples subjected to different doses of ionizing radiation. It appears that when the lifetime is presented in the Arrhenius form, a progressively diminishing activation energies toward room temperature was observed. After combining experimental OIT (oxidative induction time) data of up to about 8 years, a conservative estimate of durability of about 30 years was obtained. # 2000 Published by Elsevier Science B.V.
Metallocene polymerized ultralow density polyethylenes (ULDPE) were found to be effective impact ... more Metallocene polymerized ultralow density polyethylenes (ULDPE) were found to be effective impact modi®ers for rigid matrices such as polypropylene (PP). This is mainly due to the very high level of comonomer incorporation with homogeneous short chain branching distributions (SCBD) brought about by the single site metallocene catalysts. However, a very heterogeneous Ziegler Natta copolymer of 0.88 speci®c gravity was found to be surprisingly effective in impact modi®cation ef®ciency.
Journal of Biomaterials Science-polymer Edition, 1993
Controlled release systems of theophylline, proxyphylline and oxprenolol.HCl exhibiting modulated... more Controlled release systems of theophylline, proxyphylline and oxprenolol.HCl exhibiting modulated drug delivery were prepared by using pH-sensitive anionic copolymers of 2-hydroxyethyl methacrylate with acrylic acid or methacrylic acid. Drug release studies were carried out in simulated biological fluids. The initial drug release rates and the drug release mechanisms were dependent upon the pH and ionic strength of the buffer solution as well as its salt composition. Initial drug diffusion coefficients in these swelling-controlled release systems were calculated from the release curves; they were of the order of 10(-7) cm2/s and were dependent upon the degree of swelling. The drug release mechanism was non-Fickian in all the dissolution media studied. Lowest release rates were observed for drug release from nonionized polymer networks in agreement with the relationship between ionization, swelling and drug release.
There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs... more There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved bioavailability, nanoparticles can also provide targeting capabilities when injected intravenously. The latter property has led to increased research and development activities for intravenous suspensions. The first intravenously administered nanoparticulate product, Abraxane (a reformulation of paclitaxel), was approved by the FDA in 2006. Additional clinical trials have been conducted or are ongoing for multiple other indications such as oncology, infective diseases, and restenosis. This article reviews various challenges associated with developing intravenous nanosuspension dosage forms. In addition, various formulation considerations specific to intravenous nanosuspensions as well as reported findings from various clinical studies have been discussed.
In order to further our understanding of polymer durability, the degradation kinetics of a series... more In order to further our understanding of polymer durability, the degradation kinetics of a series of polymers was studied. The Arrhenius activation energy was used as the parameter to follow the rate dependence as a function of temperature. For most systems, it was evident that the apparent activation energies increase monotonically with temperature. This ®nding explains the frequent observation that kinetic parameters obtained at high temperatures often lead to grossly optimistic estimates of shelf life at ambient conditions. The activation energies of polypropylene from the surface embrittlement processes were also found to have a striking similarity to the thermal processes, with nearly identical activation energies at the same temperature. A good understanding of this observation could lead to broader applications and further the understanding of polymer degradation. # 2001 Published by Elsevier Science B.V.
Since the development of the oxidative induction time (OIT) test by former Bell Telephone Laborat... more Since the development of the oxidative induction time (OIT) test by former Bell Telephone Laboratories researchers, there have been many studies to broaden its applicability to polymers beyond the original polyole®ns. The basic premise in OIT studies is that a detectable oxidation onset is based on the differential reactivity between the polymer matrix and free radical scavenging antioxidants like hindered phenols. This situation does not exist in depolymerizing systems such as polymethylmethacrylates (PMMA), so many researchers concluded that a correlation did not exist for these systems. We will report on the observation of a clear cut, Arrhenius-like oxidative induction time behavior in a toughened PMMA system with high pressure DSC. The relationship between the observed OIT at elevated temperatures and high oxygen pressures with lower temperature oven aging studies will be presented. #
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Papers by Atul Khare