Hossein Omidian

Synthesis of fast-swelling superabsorbent hydrogels: effect of crosslinker type and concentration on porosity and absorption rate

Fast-swelling highly porous superabsorbent hydrogels were synthesized through a rapid solution polymerization of concentrated partially neutralized acrylic acid under normal atmospheric conditions. Acetone and sodium bicarbonate were used as porosity generators (porogens) during polymerization process for porosity generation. N,N′-methylenebisacrylamide (MBA) and 1,4-butanedioldiacrylate were used as the water- and the oil-soluble crosslinkers, respectively. The temperature changing of the reaction mixture during polymerization and foam formation process was monitored and investigated in details. Time and sequence of addition of the porogens and gelation time were recognized to be important to increase efficiency of the porogens. The concentration of the crosslinkers on gelation time was optimized to achieve highly porous products. It was found that higher crosslinker concentration, especially in the case of MBA, causes decreased gelation times. Shorter gelation time resulted in more porogen bubbles trapped in the viscose reaction mixture led to products with higher porosity. The effect of type and concentration of the crosslinking agents on the process and swelling behavior of the hydrogels (in water and saline solutions) were investigated. Power law relationships were found for the variation of swelling in terms of either crosslinker or saline concentration. Less sensitivity to the change of salinity was achieved by employing higher amount of crosslinker.

Recent developments in superporous hydrogels

Superporous hydrogels (SPHs) were originally developed as a novel drug delivery system to retain drugs in the gastric medium. These systems should instantly swell in the stomach and maintain their integrity in the harsh stomach environment, while releasing the pharmaceutical active ingredient. For years, the synthetic features and properties of these SPH materials have been modified and improved to meet the requirements for gastric retention applications. Furthermore, an instant swelling hydrogel has also shown potential application for peroral intestinal peptide and protein absorption. This review discusses the formulation, characterization, properties and applications of these polymers.

Introduction to Hydrogels

Hydrogels are a class of crosslinked polymers that, due to their hydrophilic nature, can absorb large quantities of water. These materials uniquely offer moderate-to-high physical, chemical, and mechanical stability in their swollen state. The structure of a hydrogels can be designed for a specific application by selecting proper starting materials and processing techniques. Since the equilibrium swelling capacity of a hydrogels is a balance between swelling and elastic forces, hydrogels with different swelling capacities can be designed by modulating the contribution of individual forces. Certain hydrogels respond to the changes in environmental factors by altering their swelling behavior. This chapter explains the evolution of hydrogels as a new class of the crosslinked polymers, the hydrogels structures, swelling forces, swelling kinetics, types of water in a swollen hydrogels, and composite properties of hydrogels materials.

Current approaches in tamper-resistant and abuse-deterrent formulations

Context: The escalating abuse of prescription drugs has recently spawned the development of novel drug formulations resistant to various methods of tampering and misuse. Objective: The intent of this paper is to provide an overview and classification system of formulation approaches, developed to produce what most refer to as abuse-deterrent or tamper-resistant dosage forms. Methods: A comprehensive literature search was conducted within Embase™ and Medline using key words “abuse deterrentâ and “tamper resistantâ to identify relevant technologies. Only issued patents were examined using the phrase “abuse deterrent compositionâ searched through PatFT from the United States Patent and Trademark Office. Current information from press releases and product innovator websites was obtained for additional data. Results: Identified formulation approaches were organized into two categories, physical approaches and chemical approaches. Physical approaches were subcategorized into solids, gels or non-intentionals, while chemical approaches were further broken down into agonists/antagonists, aversives, or metabolics. Among issued patents specifying an abuse-deterrent method, nine diverse approaches were found. Most formulations under development combined approaches, and utilized proprietary technologies from pharmaceutical manufacturers. Conclusions: Prodrug and agonist/antagonist formulations are popular in marketed products, while solid and gel approaches are more recent additions. However, the inclusion of aversive agents or enzyme inhibitors in a product is proving to be more difficult to develop. Overall, detailed formulation and manufacturing methods still remain rather elusive to protect public health. Moreover, these innovative formulations are mostly untried in the general population and their abuse deterring effects has yet to be proven.

DSC studies on synthesis of superabsorbent hydrogels

Abstract Reaction scheme of acrylic-based superabsorbing polymers was monitored by a differential scanning calorimeter. Differential scanning calorimetry (DSC) was used to study the heat effects during the polymer synthesis in DSC pan as a micro-scale reactor. Two distinct observations, i.e. inhibition period (IP) and onset of gel formation were recorded during polymerization. The effect of reaction temperature and initiator (K2S2O8) concentration was assessed on these general observations. It was found that unrestricted access of the reaction mixture to oxygen and unrestricted loss of water could complicate the polymerization behavior of sodium acrylate in aqueous system. A conceptual kinetic approach was followed to describe the complex process. Finally, DSC observations were compared with their corresponding bench-scale figures.

Drug delivery applications for superporous hydrogels.

Introduction: Considerable advances have been made to hydrogels with the development of faster swelling superporous hydrogels (SPHs). These new-generation hydrogels have large numbers of interconnected pores, giving them the capacity to absorb large amounts of water at an accelerated rate. This gives SPHs the ability to be used in a variety of novel drug delivery applications, such as gastric retention and peroral intestinal delivery of proteins and peptides. Areas covered: This review focuses on the applications of SPHs for drug transport and targeted drug therapies, as well as the characteristics and historical advancements made to SPH synthesis as it pertains to drug delivery. Manufacturing considerations and challenges that must be overcome are also discussed, such as scale-up, biocompatibility and safety. Expert opinion: Modern SPHs have high swelling and high mechanical strength making them suitable for many diverse pharmaceutical and biomedical applications. However, demonstrative preclinical animal studies still need to be confirmed in human trials, to further address safety issues and confirm therapeutic success when using SPHs as platforms for drug delivery. The focus of forthcoming applications of SPHs is likely to be in the area of oral site-specific delivery and regenerative medicine.

Swelling and Mechanical Properties of Modified HEMA-based Superporous Hydrogels

Superporous hydrogels (SPHs), based on poly(2-hydroxyethyl methacrylate) (PHEMA), were prepared by adding minute amounts of an ion-complexable hydrophilic acrylic acid. PHEMA SPHs are generally strong, but their swelling is minimal. To improve the swelling, different poly(HEMA-co-acrylic acid) hydrogels were polymerized and crosslinked, then physically treated with divalent calcium and trivalent aluminum cations. The incorporation of acrylic acid copolymer into the SPH, followed by crosslinking of the copolymer with calcium or aluminum ions produced SPHs with improved swelling and strength. Cells in the presence of hydrogel showed high viability indicating the absence of cytotoxicity and stimulatory effect.

Polyvinyl Alcohol in Medicine and Pharmacy: A Perspective

Polyvinyl alcohol (PVOH) is a synthetic hydrophilic linear polymer that generally exists as a copolymer of vinyl alcohol and vinyl acetate. Therefore, the structural properties of PVOH polymers primarily depend on the degree of polymerization and the degree of hydrolysis, i.e., the ratio of the two monomers. Due to reactive functional groups on its structure, PVOH undergoes chemical changes such as esterification and etherification, as well as physical changes such as crystallization and ion-polymer complexation. Both chemically and physically-modified PVOH structures have found applications in biomedical and pharmaceutical area. This article reviews the properties of PVOH in solid and solution states, PVOH hydrogels and cryogels, their biomedical and pharmaceutical applications, and their potential challenges.

Polymerization of sodium acrylate in inverse-suspension stabilized by sorbitan fatty esters

Abstract This paper is devoted the synthesis of poly(sodium acrylate) by an inverse-suspension polymerization technique. Ammonium persulfate, ethylcellulose and toluene were used as initiator, suspending agent, and continuous organic phase, respectively. Two surfactants, sorbitan monooleate (SMO) and sorbitan monostearate, were used as the suspension stabilizers. The effect of the initiator concentration as well as the type and concentration of the surfactant on the polymer molecular weight and solution viscosity was investigated. Participation of the unsaturated surfactant (SMO) in the free radical polymerization was recognized to be the main reason of enhancement of the average molecular weight and viscosity of the products. A similar effect was observed when the polymerization reactions were run in the presence of air. In the latter conditions, however, an inhibition effect of atmospheric oxygen resulted in substantially decreased solution viscosity. Meanwhile, it was found that higher polymers were obtained when the as-synthesized beads were dewatered and hardened in methanol rather than in acetone.

Abuse-deterrent formulations: Part 2: commercial products and proprietary technologies

Introduction: Increased misuse and abuse of prescription pain medications has driven extensive research and development to produce what are best known as abuse-deterrent formulations (ADFs). The ADFs are intended to prevent, impede or discourage physical and chemical tampering while still being able to provide safe and accurate delivery of an abusable medication for therapeutic benefit. Areas covered: This review primarily focuses on patents and company literature regarding the formulations, manufacturing and physiochemical properties of abuse-deterrent compositions. Also included are journal articles with relevance to the development of these novel technologies. Particular attention is given to oral dosage forms with applications found in prescription drug products, over-the-counter medications and proprietary technologies in development. Overall, the formulations of 14 drug products, 2 meth-resistant cold products and 17 pharmaceutical proprietary technologies are explored in detail. Expert opinion: Despite the introduction of a wide range of formulation and technology interventions with different deterrence potential, the progression of these technologies seems to be moving from inhibiting only one type of abuse to stopping multiple types of tampering methods. Information on inherent strengths and weaknesses of various formulations can be utilized in the development of more robust and resistant ADF in the future.