Papers by Syed A. A. Rizvi, MD, PhD (Pharm), PhD (Chem), MPH, MBA, MS, MSc, BSc, BSN, FRSM.
Journal of Nanomedicine & Nanotechnology, 2014
Oral extended-release delivery of Biopharmaceutics Classification System (BCS) class II and III c... more Oral extended-release delivery of Biopharmaceutics Classification System (BCS) class II and III compounds is desirable in order to decrease dosing frequency and potential adverse effects. Maintaining an extended-release profile of the drug is ideal to minimize fluctuations in plasma concentrations. The main objective of this research was to formulate a polymeric microsphere drug delivery system that will effectively provide extended-release characteristics via an orally administered capsule. Using acetaminophen and ibuprofen as model drugs, this drug delivery system was shown to provide extended-release characteristics of the drug for enhanced efficacy. The biodegradable polymeric matrix was formulated using bovine serum albumin (BSA) with glutaraldehyde as the crosslinker. The drug of interest was then encapsulated into the polymeric matrix and spray-dried into microspheres. Once prepared, the drug-loaded microsphere powder was placed into hard gelatin capsules. The physicochemical properties of the microsphere formulations were characterized. Additionally, differential scanning calorimetry was utilized to examine the thermal stability of the encapsulated drug. Release studies were conducted in vitro to examine the release profile of the drug. Cell uptake studies were carried out to examine the internalization capability of microsphere formulations. Drugloaded microspheres were found to be approximately 2 microns in size and exhibited a uniform size distribution. Zeta potential measurements were shown to be approximately-30 mV, which indicated that the microspheres are stable in dispersions. Release data showed a constant release of the drug from the microsphere and capsule formulations for at least 16 hours. Formulated microspheres were able to be internalized into human intestinal Caco-2 cells. These data provided evidence for the role of the microsphere delivery system in the extended-release delivery of BCS Class II and III drug substances. not limited to, hydrophilic matrix systems, coated beads or granules, inert plastic matrix systems, complex formation, and diffusion-mediated osmotic pump systems [8]. Despite some progress, oral extendedrelease drug products have not yet reached their full potential in the clinic. Conventional technologies have low drug loading capacity, high production costs, or laborious production steps [4,9]. Consequently, our research aimed to develop oral extended-release capsule formulations using the microsphere drug delivery system. Microspheres are particles often composed of an outer polymeric matrix layer of either synthetic or natural components, such as albumin, gelatin, or poly-lactic-coglycolic acid (PLGA) [10,11]. Albumin, the carrier protein used in this present study, is an ideal component of microsphere particles due to its purity, ease of incorporation, stability, modification of drug release, and antigenicity [12]. Microspheres fall in the range of 1-1000 microns in diameter. There are a number of advantages to utilizing microspheres as the technology of choice, including prolonged in vivo half-life, decreased generalized drug toxicity, improved patient compliance, and increased stability [13-18].
Education 3-13, 2013
The essay deals with sentence structure, style, and logical flow when writing scientific text. Te... more The essay deals with sentence structure, style, and logical flow when writing scientific text. Ten suggestions for optimizing sentences are presented followed by ten published examp les of stylistic variations. Although the emphasis is on chemistry, the reco mmendations are applicable to all areas of non-fiction writ ing.
Journal of the American Chemical Society, Jul 8, 2009
Molecular areas of soluble films at the air/water interface have traditionally been calculated by... more Molecular areas of soluble films at the air/water interface have traditionally been calculated by applying the Gibbs equation to the steep linear decline in surface tension as the bulk concentration increases. This approach presupposes that the interface is saturated in the "Gibbs region," thereby allowing a single unique area to be calculated. We show that the areas derived by the Gibbs equation (typically 50-60 Å 2 /molecule) are much too large to account for the abrupt surface tension decline. Moreover, a surface tension/concentration plot was observed for a system where micelle formation does not interfere with the Gibbs region. Nonetheless, the surface tension plot leveled off, ostensibly owing to saturation, when the Gibbs approach predicted a continued linear decline, proving that the interface in the Gibbs region is not saturated as generally assumed. This conclusion means that the hundreds of published molecular areas obtained by the Gibbs approach should be reconsidered. Plots of surface tension vs. ln [surfactant] display three regions (Figure 1): 1 Region-A, where the surface tension hardly changes wi th concent rat ion; Region-B, a steep, almost linear,
The research presented in this dissertation involves the synthesis, characterization, and applica... more The research presented in this dissertation involves the synthesis, characterization, and application of novel anionic and cationic chiral molecular micelles in capillary electrophoresis (CE) for the separation of diverse chiral compounds. Chapter 1 presents brief overview of the surfactants, micelle polymer, CE and micellar electrokinetic chromatography (MEKC). Chapter 2 describes the simultaneous enantioseparation of The work with this dissertation has been extensive and trying, but exciting, instructive, and fun. This dissertation could not have been possible without Dr. Shahab A. Shamsi who not only served as my supervisor but also encouraged and challenged me throughout my stay in his lab. He and the other committee members (Drs. Gabor Patonay and Lucjan Strekowski) as well as other faculty in the Department of Chemistry, Georgia State University thoroughly guided me, never accepting less than my best efforts. I thank them all. It has been a pleasure working with my colleagues, in particular, Rashid Iqbal (Georgia Pacific), Dean Norton (Metametrix Clinical Laboratory), Jack Zheng, Kerry Norton (Altea Therapeutics Corporation), David Nicholas Simons, Dr. Jingguo Hou and Dan Spratt. Also, I am especially thankful to Dr. Cevdat Akbay (Fayetteville State University) for his kind and sincere help, patience, thoughtful advice and constant support. I am deeply grateful to all of them for investing time and energy discussing creative ideas with me. Dean Norton and William Bragg deserve credit for reading sections of my work. Their incisive comments and command of vocabulary made me rethink how I presented my ideas. I will also give special thanks to Dr.
Analytical Chemistry, Sep 7, 2006
Two amino acid derived (leucinol and N-methyl pyrrolidinol) chiral ionic liquids are synthesized ... more Two amino acid derived (leucinol and N-methyl pyrrolidinol) chiral ionic liquids are synthesized and characterized both in monomeric and polymeric forms. Leucinol based chiral cationic surfactant is room a temperature ionic liquid (RTIL), and pyrrolidinol based chiral cationic surfactant melts at 30-35 °C to form ionic liquid (IL). The monomeric and polymeric ILs are thoroughly characterized to determine critical micelle concentration, aggregation number, polarity, optical rotation and partial specific volume. Here in, we present the first enantioseparation using chiral IL as pseudostationary phase in capillary electrophoresis. Chiral separation of two acidic analytes, (±)-alpha-bromophenylacetic acid (±)-(α-BP-AA) and (±)-2-(2-chlorophenoxy)propanoic acid(±)-(2-PPA) can be achieved with both monomers and polymers of undecenoxy carbonyl-L-pryrrolidinol bromide (L-UCPB) and undecenoxy carbonyl-L-leucinol bromide (L-UCLB) at 25 mM surfactant concentration using phosphate buffer at pH 7.50. The chiral recognition seems to be facilitated by the extent of interaction of the acidic analytes with the cationic head group of chiral selectors. Polysodium Nundecenoxy carbonyl-L-leucine sulfate (poly-L-SUCLS) and polysodium N-undecenoxy carbonyl-L-leucinate (poly-L-SUCL) were compared at high and low pH for the enantioseparation of (±)-(2-PPA). At pH 7.5, poly-L-SUCLS, poly-L-SUCL and ±-2-PPA are negatively charged resulting in no enantioseparation. However, chiral separation was observed for (±)-(2-PPA) using poly-L-SUCLS at low pH (pH 2.00) at which analyte is neutral. The comparison of chiral separation of anionic and cationic surfactants demonstrates that the electrostatic interaction between the acidic analyte and cationic micelle plays a profound role in enantioseparation.
European Journal of Chemistry, 2011
Micellar electrokinetic chromatography (MEKC) is a useful branch of capillary electrophoresis (CE... more Micellar electrokinetic chromatography (MEKC) is a useful branch of capillary electrophoresis (CE) that utilizes surfactant above critical micelle concentration (CMC) as pseudo-stationary phase. MEKC can be employed to separate both charged and neutral molecules, individually or simultaneously, including chiral compounds. MECK benefits from high peak efficiency due to electroosmotic flow (EOF) in the separation capillary, compounded with large variety of synthetic surfactants, organic modifiers, temperature and variable separation voltage has made MECK the method of choice for separation scientists. In this review, we present the introduction of CE, fundamentals of surfactant chemistry as it relates to MEKC, separation principles in MECK including equations involved in calculating separation parameters (capacity factor, resolution etc.). Capillary electrophoresis Electroosmotic flow Micellar electrokinetic chromatography Surfactants Critical micelle concentration Polymeric surfactants Water loving Polar Head Group Water Hating Hydrocarbon Tail
Analytical Chemistry, 2007
In this work, three amino acids derived (L-leucinol, L-isoleucinol and L-valinol) sulfated chiral... more In this work, three amino acids derived (L-leucinol, L-isoleucinol and L-valinol) sulfated chiral surfactants are synthesized and polymerized. These chiral sulfated surfactants are thoroughly characterized to determine critical micelle concentration, aggregation number, polarity, optical rotation and partial specific volume. For the first time the morphological behavior of polymeric sulfated surfactants is revealed using cryogenic high-resolution electron microscopy (cryo-HRSEM). The polysodium N-undecenoyl-L-leucine sulfate (poly-L-SUCLS) shows distinct tubular structure, while polysodium N-undecenoyl-L-valine sulfate (poly-L-SUCVS) also shows tubular morphology but without any distinct order of the tubes. On the other hand, polysodium N-undecenoyl-Lisoleucine sulfate (poly-L-SUCILS) displays random distribution of coiled/curved filaments with heavy association of tightly and loosely bound water. All three polymeric sulfated surfactants are compared for enantio-separation of broad range of structurally diverse racemic compounds at very acidic, neutral and basic pH conditions in micellar electrokinetic chromatography (MEKC). A small combinatorial library of 10 structurally related phenylethylamines (PEAs) is investigated for chiral separation under acidic and moderately acidic to neutral pH conditions using an experimental design. In contrast to neutral pH conditions, at acidic pH, significantly enhanced chiral resolution is obtained for class I and class II PEAs due to the compact structure of polymeric sulfated surfactants. It is observed that the presence of hydroxy group on the benzene ring of PEAs resulted in deterioration of enantioseparation. A sensitive MEKC-mass spectrometry (MS) method is developed for one of the PEA (e.g., (±)-pseudoephedrine) in human urine. Very low limit of detection (LOD) is obtained at pH 2.0 (LOD 325 ng/mL), which is ca 16 times better compared to pH 8.0 (LOD 5.2 µg/mL). Other broad range of chiral analytes (β-blockers, phenoxypropionic acid, benzoin derivatives, PTHamino acids, and benzodiazepinones) studied also provided improved chiral separation at low pH compared to high pH conditions. Among the three polymeric sulfated surfactants, poly-L-SUCILS with two chiral centers on the polymer head group provided overall higher enantioresolution for the investigated acidic, basic and neutral compounds. This work clearly demonstrates for the first time the superiority of chiral separation and sensitive MS detection at low pH over conventional high pH chiral separation and detection employing anionic chiral polymeric surfactants in MEKC and MEKC-MS.
Current Overview on Pharmaceutical Science Vol. 9, Apr 5, 2023
Medical Research Archives
Recently, the nasal cavity has been highlighted as an ideal route of administration for intervent... more Recently, the nasal cavity has been highlighted as an ideal route of administration for interventions as it is the portal of entry of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The present study aimed to demonstrate the feasibility and efficacy of intranasally administered Chlorpheniramine Maleate (CPM) spray to treat coronavirus disease 2019 (COVID-19). Methods: The present study used a two-phase, non-clinical to clinical approach. The non-clinical phase evaluated CPM’s antiviral activity against SARS-CoV-2 delta (B.1.617.2) strain via a highly differentiated three-dimensional in vitro model of normal, human-derived tracheal/bronchial epithelial cells. CPM was tested in duplicate inserts of the tissue models of the human airway. Virus yield reduction assays measured antiviral activity on day six after infection. For the clinical phase, COVID-19 symptomatic (polymerase chain reaction positive) patients were recruited and assigned to a 7-day CPM treatment (n=32) ...
Cureus
It is well known that acute COVID-19 infection can present with a variety of symptoms, including ... more It is well known that acute COVID-19 infection can present with a variety of symptoms, including fever, cough, rhinitis, loss of taste, and the cardinal sign of loss of smell (anosmia). Recently, nasal irrigations with saline and other agents have shown promise for the treatment of COVID-19. Xylitol has been shown to display virucidal effects against SARS-CoV-2. This study aimed to examine the efficacy of xylitol as an adjunct treatment for COVID-19 in an outpatient setting. In a randomized controlled double-blinded fashion, a total of 50 participants (F=30) consented to participate in this study. It was a population of 18 to 65 years of age, with polymerase chain reaction confirmed for SARS-COV-2 by nasopharyngeal swab, less than three days from the start of symptoms. This study's primary endpoint was time to clinical recovery, defined as the change from baseline to end of treatment in COVID-19 symptoms. Outcome variables were the changes in visual analog scale (VAS) and daily symptoms score (DSS) on Days 1-7, 14, and 28 after the initiation of the 14-day treatment. There were no differences between the treatment groups in any demographic and subject characteristics-related variables, including vaccination status. None of the patients were hospitalized, or required emergency visits in addition to no adverse reactions were reported. There were no statistically significant interactions found for VAS (P=0.124), DSS (P=0.448), and sense of smell (P=0.667). The proportion of patients reporting nasal congestion was higher (X 2 =5.05; P=0.025) in the xylitol (XYL) group (73.1%) vs. the saline (SAL) group (41.7%) on Day 4, and on Day 7 (X 2 =5.72; P=0.017) XYL group (50.0%) vs. SAL group (17.4%). During Day 28 a total of two patients in the SAL group had anosmia vs. no patients with anosmia in the XYL group, although this difference did not reach statistical significance (X 2 =5.72; P=0.133). Results demonstrate that both xylitol and saline were equally effective in decreasing the time of symptom resolution and preventing hospitalizations, yet, persistent anosmia was only seen in the SAL group. Intranasal xylitol might play a pivotal role in preventing persistent olfactory abnormalities in post-COVID-19 patients.
Consultant, 2021
report no direct compensation or grant funding was received for this article. The authors report ... more report no direct compensation or grant funding was received for this article. The authors report that they are medical and scientific advisers to USA Equities Corp, the developer of the allergy management evaluation digital survey. Grogan reports being a director, officer, and having equity ownership in USA Equities Corp, a company that develops and makes products related to the digital applications reported in this article.
Journal of Chromatography A, 2010
Two cationic gemini surfactants with pyrrolidinium or alkyl ammonium head groups with but-2-yne s... more Two cationic gemini surfactants with pyrrolidinium or alkyl ammonium head groups with but-2-yne spacers, but with the same length hydrocarbon chain have been characterized with respect to their aggregation behaviors and separation power as pseudostationary phases (PSPs) for micellar electrokinetic chromatography (MEKC). They were compared with a commonly used PSP, sodium dodecylsulfate (SDS). The results suggest that the head groups of the surfactants have some effect on physicochemical properties such as critical micelle concentration (CMC), C 20 , CMC , partial specific volume, methylene selectivity and mobilities of the surfactants. CMC values of G1, G2 and SDS in pure water were found to be 0.82, 0.71, and 8.08 mM, respectively; they were reduced to 0.21, 0.11, and 3.0 mM when measured in 10 mM phosphate buffer at pH 7.0. G1 (˛C H 2 = 2.74) and G2 (˛C H 2 = 2.48) provided the most and the least hydrophobic environment, respectively. According to their partial specific volumes, geminis were found to have more flexible structures as compared with sodium dodecylsulfate. The effects of the head group structure were also characterized with the linear solvation energy relationship (LSER) model, which was able to evaluate the role of solute size, polarity/polarizability, and hydrogen bonding on retention and selectivity. The cohesiveness, hydrogen bond acidic and basic character of the surfactant systems were found to have the most significant influence on selectivity and MEKC retention of the gemini surfactants. It should be noted that with their large positive coefficient a values, G1 and G2 were found to be stronger HB acceptors than anionic and most of the cationic surfactants studied in the literature.
ELECTROPHORESIS, 2005
Glycine-based polymeric surfactants with varied polar head group: II. Chemical selectivity in mic... more Glycine-based polymeric surfactants with varied polar head group: II. Chemical selectivity in micellar electrokinetic chromatography using linear solvation energy relationships A series of four acyl and four alkenoxy glycinates (i.e., mono-, di-, tri-, and tetraderivatives of polysodium N-undecenoyl glycinate (poly-SUGs) as well as polysodium N-undecenoxy carbonyl glycinates (poly-SUCGs)) were compared for simultaneous separation of nonhydrogen bonding (NHB), hydrogen-bond acceptor (HBA), and hydrogen-bond donor (HBD) solutes. An increase in the number of glycine units in the polar head group of polymeric surfactant decreases both the retention and the migration window of all solutes with some changes in separation selectivity. The poly(sodium N-undecenoxy carbonyl-glycinate) (poly-SUCG 1) with one glycine unit was the least polar surfactant and has the lowest phase ratio, but this monoglycinate surfactant provided the best simultaneous separation of 10-NHBs and 8-HBAs. On the other hand, 9-HBDs were well separated using any of the six mono-, di-, and triglycinate surfactants compared to the two tetraglycinates. Linear solvation energy relationships (LSERs) and separation of the geometrical isomers studies were also performed to further envisage the selectivity differences. From LSER studies, the phase ratio and hydrogen-bond-donating strength of the poly-SUG series of surfactant were found to increase with an increase in the size of the head group, but no clear trends were observed for poly-SUCG surfactants. The cohesiveness for all poly-SUG and poly-SUCG was positive, but the values were generally lower (with exception of the poly(sodium N-undecenoyl glycyl-glycyl-glycinate)) at a higher number of glycine units. Finally, the poly(sodium N-undecenoyl glycinate) and poly-SUCG 1 were found to be the two best polymeric surfactants as they provided relatively higher shape selectivity for separation of two of the three sets of geometrical isomers.
Analytical Chemistry, 2005
The feasibility of using a new and more versatile polymeric chiral surfactant, i.e., poly(sodium ... more The feasibility of using a new and more versatile polymeric chiral surfactant, i.e., poly(sodium N-undecenoxy carbonyl-L-leucinate (poly-L-SUCL) is investigated for simultaneous enantioseparation and detection of eight structurally similar-blockers with tandem UV and MS detection. Three optimization approaches, i.e., direct infusion-MS, capillary zone electrophoresis-MS, and chiral micellar electrokinetic chromatography-mass spectrometry (CMEKC-MS), were investigated to optimize sheath liquid parameters, spray chamber parameters, and CMEKC separation parameters for maximum sensitivity and chiral resolution. Compared to unpolymerized micelle of L-SUCL, the use of micelle polymer (i.e., poly-L-SUCL) provided significantly higher separation efficiency, lower separation current, and higher detection sensitivity for CMEKC-ESI-MS of-blockers. It was also observed that, unlike monomeric L-SUCL, polymeric L-SUCL provided enantioseparation of all-blockers even at the lowest surfactant concentration (i.e., 5 mM poly-L-SUCL). Under optimum CMEKC and ESI-MS conditions (15 mM poly-L-SUCL, 25 mM each of NH 4 OAc and TEA (pH 8.0); 80% (v/v) methanol sheath liquid containing 40 mM NH 4 OAc (pH 8.0); sheath liquid flow rate, 5.0 µL/min; drying gas flow rate, 5 L/min; drying gas temperature, 200°C; nebulizing pressure, 6 psi (0.414 bar); capillary voltage, +2.5 kV; fragmentor voltage, 85 V), baseline enantioseparation of eight-blockers was achieved by tandem UV (in ∼30 min) and MS (in ∼60 min) detection. Calibration curves for all-blockers were linear in the range of 0.01-0.6 mM for both CMEKC-UV and CMEKC-MS methods, but the later method provided better concentration limit of detection with similar RSD for migration time and peak areas. The CMEKC-ESI-MS method appears suitable for use as a routine procedure for high-throughput separation of-blockers with high sensitivity.
Sci, Apr 8, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Sci, Apr 9, 2019
Nizatidine is a gastroprotective drug with a short biological half-life and narrow absorption win... more Nizatidine is a gastroprotective drug with a short biological half-life and narrow absorption window. This study aimed at developing floating tablets of nizatidine using various HPMC viscosity grades, namely K4M, E4M, K15 and K200M. Directly compressed tablets revealed an excellent uniformity in hardness, thickness and weight and nizatidine was evenly distributed within the matrix floating tablets. Buoyancy study revealed floating lag time as low as 18-38 s, and tablets remain buoyant for upto 24 h. However, the later depended upon viscosity grade of HPMC and that the higher the viscosity, the less was the total floating time. In vitro dissolution indicated viscosity dependent nizatidine release from the floating tablets. HPMC K4M and E4M based floating tablets released almost 100% drug in 12 h, whilst higher viscosity polymers such as K15 and K200M only released 81.88% and 75.81% drug, respectively. The drug release followed non-Fickian diffusion from tablets formulated with K4M, K15 and K200M, whilst super case II transport was observed with E4M based tablets. More interestingly, K4M and E4M polymers have similar viscosity yet exhibited different drug release mechanism. This was attributed to the difference in degree of substitution of methoxyl-and hydroxypropoxyl-groups on polymer backbone.
Background: Recently, nasal drug delivery has emerged as a convenient modality for the treatment ... more Background: Recently, nasal drug delivery has emerged as a convenient modality for the treatment of multiple, allergic, infectious, and inflammatory sinonasal conditions. Some patients report discomfort and irritation associated with the pressure and flow generated by using typical atomizers which may lead to decrease patient compliance and lower satisfaction. We sought to develop a rather gentle atomizer for nasal irrigation that would ameliorate the discomfort associated with nasal drug delivery. Herein, we report the development of an atomizer via fluid dynamics modeling and evaluating the patient experience.Methods: Using computational flow dynamics modeling, we assessed the distribution of atomized droplets to compare the conventional narrow-angle (NA) Vs a new open-angle swirling effect (OSE) atomizer. The goal for the new atomizer was to generate a swirling effect by opening a spray cone from a tapered nozzle bottle at different head tilted positions to determine the most eff...
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Papers by Syed A. A. Rizvi, MD, PhD (Pharm), PhD (Chem), MPH, MBA, MS, MSc, BSc, BSN, FRSM.