Alekha K Dash

Creighton University, Omaha, NE, United States

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Publications (38)99.56 Total impact

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    Alekha K Dash, Angeli Sawhney
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    ABSTRACT: The objective of this study was to develop a simple and sensitive LC method for the determination of creatine and creatinine in various creatine supplement formulations. The chromatographic system comprised of a LC-600 pump, SCL-6B system controller, and SPD-6AV detector (Shimadzu, Japan). The mobile phase consisted of 0.045 M ammonium sulfate in water. The chromatographic separation was achieved at ambient temperature on a Betabasic C-18 column (250 x 4.6 mm, Keystone Sci.). The flow rate was maintained at 0.75 ml/min and effluents are monitored at 205 nm. 4-(2-Aminoethyl)benzene sulfonamide was used as an internal standard (IS). This method required less than 7 min of chromatographic time. The standard curves were linear over the concentration range of 1-100 microg/ml for creatine and 2-100 microg/ml for creatinine, respectively. The relative standard deviations (RSD) for the within-day and day-to-day precision for creatine were within 1.0-4.6 and 2.2-4.7%, respectively. The RSD for the accuracy of creatine assay was in the range of 2.4-4.7%. The RSD values for the within-day precision, day-to-day precision and accuracy for creatinine validation were 1.7-4.4, 2.3-5.4 and 2.4-4.8%, respectively. This method was used to determine: (i) the creatine concentration in various marketed products; (ii) saturated solubility of various creatine salts; and (iii) stability of creatine in aqueous solution. In conclusion, a simple and sensitive LC method with UV detection was developed for the simultaneous determination of creatine and creatinine in formulations. Di-creatine citrate salt showed a higher aqueous solubility (at 25 degrees C) as compared to creatine and creatine monohydrate. Some of the over-the-counter (OTC) products tested contained a very low level of creatine in contrast to their label claim. Substantial conversion of creatine into creatinine was noticed in liquid formulation.
    Journal of Pharmaceutical and Biomedical Analysis 08/2002; 29(5):939-45. · 2.95 Impact Factor
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    ABSTRACT: Ethylcellulose microspheres containing tolnaftate (I) were prepared by the emulsion-solvent evaporation technique. An X-ray powder diffractometric method was developed to quantify the content of crystalline I in these microspheres. X-ray lines of I with d-spacings of 5.5 and 4.2 A were chosen for the quantitative analyses. Physical mixtures containing various weight fractions of I and blank (empty) microspheres were prepared and lithium fluoride (20% w/w) was added as the internal standard. The 5.5 and 4.3 A lines of I and the 2.3 A line of lithium fluoride were used for the quantitative analysis. A plot of the intensity ratio (intensity of the 5.5 A line of I/intensity of 2.3 A line of lithium fluoride) as a function of the weight percent of I in the mixture, resulted in a straight line. The crystalline content of I in the tolnaftate-loaded microspheres was determined using this standard curve. A second independent determination of the content of I was possible from the intensities of the 4.3 A line. The enthalpy of fusion of I, determined by differential scanning calorimetry (DSC), was also used as a measure of the crystalline content of I in the microspheres. The X-ray and DSC methods measure the content of crystalline I in the microspheres at room temperature ( approximately 25 degrees C) and at the melting point of I (111 degrees C), respectively. The total content of I in the microspheres was determined by HPLC. The DSC and X-ray results indicated that a substantial fraction of the incorporated I was dissolved in the ethylcellulose matrix.
    Journal of Pharmaceutical Sciences 05/2002; 91(4):983-90. · 3.13 Impact Factor
  • Alekha K Dash, Yoonsun Mo, Abira Pyne
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    ABSTRACT: Creatine monohydrate (CM) is a nutritional supplement and an ergogenic aid for athletes. It appears to increase lean body mass, high-intensity power output and strength in healthy humans. The crystal structure of creatine monohydrate has previously been reported. However, little information is available on its solid-state properties. In this investigation, creatine monohydrate was subjected to Thermal Analyses, Karl-Fisccher Titrimetry (KFT), Scanning Electron Microscopy (SEM), and Variable Temperature X-ray Powder Diffractometry (VTXRD) to characterize its solid-state properties. The results of this study suggested that commercially available creatine monohydrate dehydrates at about 97-125 degrees C. A phase transition after dehydration was confirmed by X-ray diffraction studies. This dehydrated phase at a temperature above 230 degrees C undergoes intramolecular cyclization with a loss of an additional mole of water to form creatinine. Creatinine finally melts with decomposition at about 290 degrees C. VTXRD, confirmed that the above solid-state thermal transformation was kinetically driven, and occurred within a narrow temperature range. Mass Spectrometric (MS) studies further indicated a possible dimerization of creatinine formed during the solid-state transformation.
    Journal of Pharmaceutical Sciences 04/2002; 91(3):708-18. · 3.13 Impact Factor
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    ABSTRACT: This investigation synthesized and characterized hydroxyapatite (HAP) microspheres, agglomerated microspheres, and implants containing ciprofloxacin. This delivery system is to be used as an implantable drug delivery system for the treatment of bone infections. The HAP microspheres were made by chemical precipitation followed by a spray-drying technique. Agglomerated microspheres were prepared by a wet granulation process using a granulator. Implants were prepared by direct compression of the granules on a Carver press. Ciprofloxacin was analyzed by high-performance liquid chromatography. Characterization of the HAP microspheres include particle size, size distribution, physical state of the drug in the microsphere, and microstructure of the drug delivery system before and after in vitro release. The particle size, porosity, and morphology of the microspheres were dependent on viscosity and concentration of the slurry as well as the atomization pressure used during spray drying. Even at the highest drug load (2% wt/wt), the drug was present in a noncrystalline state. The drug release from the agglomerated microspheres was quick and almost complete within 1 hour. However, compressing the same amount of agglomerated microspheres into an implant greatly reduced the rate of ciprofloxacin release. Only 12% (wt/wt) of the drug was released from the implant within 1 hour. The in vitro release of ciprofloxacin from these implants follows a diffusion-controlled mechanism. This method provides a unique way of producing various shapes and drug loads of HAP microspheres that can be easily manufactured on a commercial scale.
    AAPS PharmSciTech 02/2002; 3(1):E1. · 1.58 Impact Factor
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    ABSTRACT: Creatine is a nutraceutical that has gained popularity in both well-trained and casual athletes for its performance-enhancing or ergogenic properties. The major disadvantages of creatine monohydrate formulations are poor solubility and oral bioavailability. In the present study, creatine transport was examined using Caco-2 monolayers as an in vitro model for intestinal absorption. Confluent monolayers of Caco-2 cells (passage 25-35) were used for the permeability studies. Monolayers were placed in side-by-side diffusion chambers. (14)C-Creatine (0.1-0.5 microCi/mL) was added to either the apical or basolateral side, and the transport of the creatine across the Caco-2 monolayer was measured over a 90-min period. The apical to basolateral transport of (14)C-creatine was small, ranging from 0.2-3% of the original amount appearing on the receiver side in a 90-min period. Interestingly, the basolateral to apical permeability of radiolabeled creatine was substantially greater than that observed in the apical to basolateral direction. Studies with drug efflux transport inhibitors indicate that neither the P-glycoprotein nor multidrug resistance-associated protein is involved in the enhanced basolateral to apical transport of creatine.
    Journal of Pharmaceutical Sciences 11/2001; 90(10):1593-8. · 3.13 Impact Factor
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    ABSTRACT: This study was designed to investigate the penetration across the blood-brain barrier of three doses of levofloxacin using a microdialysis probe implanted into the cerebrospinal fluid (CSF) of a rabbit pneumococcal meningitis model. The microdialysis guide cannula was implanted into rabbit subarachnoid space using a stereotaxic frame. After 3 days, 10(4) cfu Streptococcus pneumoniae serotype 3 in 0.3 mL saline was injected via intracisternal puncture and animals were allowed to incubate the organisms for 16-18 h. Groups of animals (n = 5) then received 7, 10.5 or 14 mg/kg iv of the drug over 10 min. Plasma samples were obtained via an ear vein 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h after the antibiotic infusion. CSF microdialysis effluent samples were collected every 0.5 h for the entire experiment. Plasma and microdialysis effluent samples were analysed by HPLC. AUC(0-8) in plasma and CSF were computed using the trapezoid rule. The elimination half-life in plasma and CSF was calculated using non-linear regression analysis. The unbound peak plasma concentrations for the three doses studied were 3.9, 6.4 and 10.3 mg/L, respectively. There was a significant increase in the plasma AUC(0-8) [29.7 +/- 6.3, 49.1 +/- 19.1 and 67.6 +/- 8.9 mg x h/L (P < 0.005)]. The unbound peak CSF concentrations were 3.8, 5.7 and 8.6 mg/L and occurred at 0-0.5 h after the administration of the dose. The AUC(CSF(0-8)) was significantly higher as the dose was increased (7 mg/kg, 15.8 +/- 6.6; 10.5 mg/kg, 37.3 +/- 7.8; and 14 mg/kg, 46.4 +/- 20.9 mg x h/L; P < 0.03). The penetration of levofloxacin averaged 53% for the 7 mg/kg dosage group, 76% for the 10.5 mg/kg group and 68% for the 14 mg/kg group. Our results demonstrate that levofloxacin penetration into the CSF averages 66% for the doses that would be used in clinical practice.
    Journal of Antimicrobial Chemotherapy 05/2001; 47(5):611-5. · 5.34 Impact Factor
  • H Fan, A K Dash
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    ABSTRACT: Doxorubicin is one of the most potent anti-tumor agents used generally in the treatment of bone cancer. Like other cancer chemotharepeutics, it produces undesirable side effects such as cardiotoxicity, which is especially severe when administrated via the conventional intravenous route. In order to minimize the systemic toxicities and to make this drug more suitable for the treatment of bone cancer, an implantable delivery system with cross-linked gelatin as the biodegradable matrix material was developed. This delivery system could possibly improve targeting of the drug as well as sustain the rate of release of the drug to the tumor. Glutaraldehyde was used as a cross-linking agent. Incorporation of glutaraldehyde in the matrix was needed to maintain the mechanical strength of the implant and to sustain the rate of release of the drug from the implant. Besides cross-linking the gelatin matrix, glutaraldehyde was found to cross-link the free amino group of doxorubicin. The effect of cross-linker concentration on the stability of the drug in the implant and on the rate and extent of release were also evaluated. In conclusion, cross-linked gelatin implants were developed for the local delivery of doxorubicin.
    International Journal of Pharmaceutics 03/2001; 213(1-2):103-16. · 3.99 Impact Factor
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    A K Dash, G C Cudworth
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    ABSTRACT: The objective of this investigation was to evaluate an acetic acid ester of monoglycerides made from edible, fully hydrogenated palm oil (AC-70) as a suppository base and compare it with a commercially available semisynthetic base (Suppocire AI). Benzocaine and miconazole were used as model drugs. Suppositories were prepared by the fusion method. The drug loads in the suppositories were kept at 2% to 5% (wt/wt). In vitro release of drug from the suppositories into Sorensen's phosphate buffer (pH 7.4) was studied using a US Pharmacopeia dissolution apparatus 1 and a spectrophotometer. The melting behavior of the bases and the physical state of the drug in the suppositories were studied using a differential scanning calorimeter (DSC). Powder x-ray diffractometry was used to study any possible polymorphic changes in the AC-70 base during formulation and storage. In vitro release studies revealed that the release of benzocaine from the AC-70 suppository was substantially slower than that of the commercial AI base. At a 2.5% (wt/wt) benzocaine load, the release of drug from the AC-70 suppositories was found to be linear. This slow and linear release was attributed to the physical property of the base, which forms liquid crystalline phases in the aqueous dissolution medium. The lyotropic liquid crystalline phase has the ability to incorporate drug into its structure and can control the release kinetics of the drug from such a system. The apparent pH of the release medium (water) was decreased by 1 to 1.5 pH units when the AC-70 base was used. The DSC studies revealed that the melting range of the AC-70 base is 36 degrees C to 38 degrees C, which is ideal for suppository formulations. The results of these studies support the possibility of using this new base for slow-release suppository formulations. This base may be of particular interest for a drug that requires an acidic environment to maintain its activity.
    AAPS PharmSciTech 02/2001; 2(3):E13. · 1.58 Impact Factor
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    ABSTRACT: Creatine is a nutraceutical that has gained popularity in both well-trained and casual athletes for its performance-enhancing or ergogenic properties. The major disadvantages of creatine monohydrate formulations are poor solubility and oral bioavailability. In the present study, creatine transport was examined using Caco-2 monolayers as an in vitro model for intestinal absorption. Confluent monolayers of Caco-2 cells (passage 25–35) were used for the permeability studies. Monolayers were placed in side-by-side diffusion chambers. 14C-Creatine (0.1–0.5 μCi/mL) was added to either the apical or basolateral side, and the transport of the creatine across the Caco-2 monolayer was measured over a 90-min period. The apical to basolateral transport of 14C-creatine was small, ranging from 0.2–3% of the original amount appearing on the receiver side in a 90-min period. Interestingly, the basolateral to apical permeability of radiolabeled creatine was substantially greater than that observed in the apical to basolateral direction. Studies with drug efflux transport inhibitors indicate that neither the P-glycoprotein nor multidrug resistance-associated protein is involved in the enhanced basolateral to apical transport of creatine. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1593–1598, 2001
    Journal of Pharmaceutical Sciences 01/2001; 90(10):1593-1598. · 3.13 Impact Factor
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    H Fausett, C Gayser, A K Dash
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    ABSTRACT: The purpose of this investigation was to develop a rapidly disintegrating calcium carbonate (CC) tablet by direct compression and compare it with commercially available calcium tablets. CC tablets were formulated on a Carver press using 3 different forms of CC direct compressed granules (Cal-Carb 4450, Cal-Carb 4457, and Cal-Carb 4462). The breaking strength was measured using a Stokes-Monsanto hardness tester. The disintegration and dissolution properties of the tablets were studied using USP methodology. The calcium concentration was determined by an atomic absorption spectrophotometer. Scanning electron microscopy was used to evaluate the surface topography of the granules and tablets. Breaking strength of Cal-Carb 4450, Cal-Carb 4457, and Cal-Carb 4462 tablets was in the range of 7.2 to 7.7 kg, as compared with a hardness of 6.2 kg and 10 kg for the commercially available calcium tablets Citracal and Tums, respectively. The disintegration time for the tablets presented in the order earlier was 4.1, 2.1, 1.9, 2.9, and 9.7 minutes, respectively. The dissolution studies showed that all formulations released 100% of the elemental calcium in simulated gastric fluid in less than 20 minutes. In summary, this study clearly demonstrated that quick disintegrating CC tablets can be formulated without expensive effervescence technology.
    AAPS PharmSciTech 02/2000; 1(3):E20. · 1.58 Impact Factor
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    ABSTRACT: The aims of this investigation were: i. to develop a rectal nicotine delivery system with bioadhesives for the treatment of ulcerative colitis and ii. to evaluate nicotine transport and cytotoxicity of the delivery system using Caco-2 cell culture systems. Rectal nicotine suppository formulations were prepared in semi-synthetic glyceride bases (Suppocire AM and AI, Gattefosse Inc.) by fusion method. The in vitro release of nicotine was carried out in modified USP dissolution apparatus 1. Differential scanning calorimetry (DSC) and powder X-ray diffraction were used to study the polymorphic changes if any in the formulations. An LC method was used for the assay of nicotine. The effect of bioadhesives (glyceryl monooleate (GMO), and Carbopol) on the nicotine flux was evaluated using Caco-2 cell permeability studies and Caco-2 cell viability was determined using the MTT toxicity assay. In vitro release studies indicated that the low melting AI base was superior to that of the AM base. Presence of GMO in the formulation enhanced the release of nicotine whereas Carbopol showed an opposite effect. The enhanced release of nicotine in the presence of GMO was found to be partly due to the melting point lowering effect of this compound. Caco-2 cell absorption studies showed that there was a decrease in the flux of nicotine in the presence of both the bioadhesives. The flux of the fluorescein marker which is used to study the integrity of the cell monolayers was found to be slightly higher only in the presence of 10% (w/w) Carbopol. Nicotine, Carbopol, and GMO do not have any cytotoxic effect on these cell monolayers within the concentration range used in the formulations. Rectal nicotine formulations containing bioadhesives were developed and characterized. Both in vitro release and cell culture studies have indicated that one can manipulate the nicotine release from these rectal delivery systems by incorporation of various bioadhesives or the use of different bases in the formulation. Nicotine concentration below 2% (w/v) and bioadhesive concentration below 10% (w/w) do not have any cytotoxic effect on Caco-2 cells.
    International Journal of Pharmaceutics 12/1999; 190(1):21-34. · 3.99 Impact Factor
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    ABSTRACT: The major challenge faced during the development of implantable dosage forms for site-specific delivery is monitoring the local concentration of the drug at or around the site of action. The tissue concentration at the site is generally measured by either sacrificing the animal at different points in time or by determining the amount of drug left in the implants at various time intervals. Unfortunately, there are no official in vitro dissolution methods available to study the release characteristics of drugs from this drug delivery system. The objective of this investigation was to develop a simple method using microdialysis sampling technique to serve as an in vitro dissolution method for implantable drug delivery systems. Ciprofloxacin implants were prepared by compressing ciprofloxacin microcapsules in poly(lactic acid) (PLA) and poly(lactic-glycolic acid) (PLGA). A sensitive HPLC method was developed and validated for the assay of Ciprofloxacin. An in vitro dissolution method was developed to study the release characteristics of drug from these implants. The method used a microdialysis sampling technique and a small sample volume of release medium. The various advantages and disadvantages of this method over other USP methods are discussed.
    Journal of Pharmaceutical Sciences 11/1999; 88(10):1036-40. · 3.13 Impact Factor
  • A M Ichwan, M Karimi, A K Dash
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    ABSTRACT: The in vitro release of a drug from topical formulations depends on the concentration of the drug in the formulation, the solubility of the drug in the base, the diffusion coefficient of the drug in the vehicle, and the partition coefficient of the drug between the vehicle, and the release medium. Incorporation of both complexing agents and cosolvents into such formulations has been used to enhance the in vitro release of a drug from topical formulations. In this investigation, a novel approach to enhance the in vitro release of benzocaine from different ointment formulations has been introduced. In this study, benzocaine was microencapsulated using gelatin-acacia complex coacervation technique. Various weight fractions of the coacervate, 5, 10, and 20% (w/w), were incorporated into both oleaginous and absorption bases. The in vitro release characteristics of benzocaine from the resulting ointments were studied using a modified USP Dissolution Apparatus 2. A plot of the cumulative amount of drug released (7-8%) per unit surface area versus (time)(1/2) was linear. Microscopic studies of the formulations revealed that the coacervates maintained their integrity in the formulation during the preparation and storage of the dosage form. Differential scanning calorimetric (DSC) studies indicated that the drug existed in the crystalline state in all formulations including those at a low drug load (0.5% w/w). DSC was also used to determine the solubility of the drug in the formulation. The rate and extent of drug release was higher in the absorption base as compared to the oleaginous base.
    Journal of Pharmaceutical Sciences 09/1999; 88(8):763-6. · 3.13 Impact Factor
  • H M Owens, C J Destache, A K Dash
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    ABSTRACT: A simple LC method was developed and validated for the analysis of ceftriaxone in aqueous and biological samples. Chromatographic separation was achieved on a reversed-phase C18 microbore column (Hypersil 5 microm, 200x2.1 mm) with UV detection at 270 nm. This isocratic system was operated at ambient temperature and required less than 10 min of chromatographic time. The flow-rate was maintained at 0.5 ml min(-1). Cetyltrimethylammonium bromide (0.01 M) was utilized as the ion-pairing agent. For the analysis of the drug in the aqueous system, the mobile phase consisted of methanol-acetonitrile-phosphate buffer, pH 7.4 (20:20:60, v/v/v). The plasma and CSF systems used the same mobile phase constituents in a slightly different ratio (30:40:30, v/v/v). Lidocaine was used as an internal standard and the peak height ratios of the drug to that of the internal standard were linear over the concentration range of 0.0 to 16 microg ml(-1) only in the case of aqueous systems. Within-day and day-to-day relative standard deviations ranged from 0.3 to 2.2% and 1.1 to 5.9%, respectively. This method was used to: (1) quantify ceftriaxone in an aqueous system, in rabbit plasma using a simple protein precipitation procedure, and in the CSF; (2) evaluate the permeability characteristics of ceftriaxone across the blood-brain barrier through quantification of ceftriaxone in the CSF using a microdialysis sampling technique; and (3) analyze the effects of dexamethasone (a synthetic fluorinated corticosteroid used for the relief of cerebral edema) on the permeability of ceftriaxone across the blood brain barrier through quantification of ceftriaxone in the dexamethasone-treated animals with meningitis.
    Journal of chromatography. B, Biomedical sciences and applications 06/1999; 728(1):97-105.
  • Alekha K. Dash, Paul W. Haney, Marc J. Garavalia
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    ABSTRACT: The major challenge faced during the development of implantable dosage forms for site- specific delivery is monitoring the local concentration of the drug at or around the site of action. The tissue concentration at the site is generally measured by either sacrificing the animal at different points in time or by determining the amount of drug left in the implants at various time intervals. Unfortunately, there are no official in vitro dissolution methods available to study the release characteristics of drugs from this drug delivery system. The objective of this investigation was to develop a simple method using microdialysis sampling technique to serve as an in vitro dissolution method for implantable drug delivery systems. Ciprofloxacin implants were prepared by compressing ciprofloxacin microcapsules in poly(lactic acid) (PLA) and poly(lactic- glycolic acid) (PLGA). A sensitive HPLC method was developed and validated for the assay of Ciprofloxacin. An in vitro dissolution method was developed to study the release characteristics of drug from these implants. The method used a microdialysis sampling technique and a small sample volume of release medium. The various advantages and disadvantages of this method over other USP methods are discussed.
    Journal of Pharmaceutical Sciences 01/1999; 88(10):1036-1040. · 3.13 Impact Factor
  • A K Dash, G C Cudworth
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    ABSTRACT: In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of drug administration, new dosage forms containing the drug(s) were introduced. As time progressed, there was a need for delivery systems that could maintain a steady release of drug to the specific site of action. Therefore, drug delivery systems were developed to optimize the therapeutic properties of drug products and render them more safe, effective, and reliable. Implantable drug delivery systems (IDDS) are an example of such systems available for therapeutic use. The application of currently available implantable drug delivery systems is the main focus of this review. IDDS can be classified into three major categories: biodegradable or nonbiodegradable implants, implantable pump systems, and the newest atypical class of implants. Biodegradable and nonbiodegradable implants are available as monolithic systems or reservoir systems. The release kinetics of drugs from such systems depend on both the solubility and diffusion coefficient of the drug in the polymer, the drug load, as well as the in vivo degradation rate of the polymer, especially, in the case of the biodegradable systems. Controlled release of drug from the implantable pump is generally achieved utilizing the microtechnology of electronic systems and remote-controlled flow rate manipulation through the maintenance of a constant pressure difference. The third atypical class includes those which have been recently developed such as ceramic hydroxyapatite antibiotic systems used in the treatment of bone infections, intraocular implants for the treatment of glaucoma, and transurethral implants utilized in the treatment of impotence. The major advantages of these systems include targeted local delivery of drugs at a constant rate, less drug required to treat the disease state, minimization of possible side effects, and enhanced efficacy of treatment. Also, these forms of delivery systems are capable of protecting drugs which are unstable in vivo and that would normally require a frequent dosing intervals. Due to the development of such sustained release formulations, it is now possible to administer unstable drugs once a week to once a year that in the past required frequent daily dosing. Preliminary studies using these systems have shown superior effectiveness over conventional methods of treatment. However, one limitation of these newly developed drug delivery systems is the fact that their cost-to-benefit ratio (cost/benefit) is too high which restricts their use over conventional dosage forms. Hopefully, in the future, new implantable systems can be developed at a lower cost, thereby minimizing the cost-to-benefit ratio and therefore, be used extensively in standard therapeutic practice. Some of the most recently discovered implants are in the early developmental stages and more rigorous clinical testing is required prior to their use in standard practice.
    Journal of Pharmacological and Toxicological Methods 08/1998; 40(1):1-12. · 2.15 Impact Factor
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    ABSTRACT: Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has been implicated in causing cerebral edema. Modulating NO production in cerebrospinal fluid (CSF) may have a role in the treatment of bacterial meningitis. Experimental S. pneumoniae meningitis was induced in a rabbit model to determine CSF parameters and NO concentrations. An electrochemical probe in the CSF throughout the 7-hour experiment monitored NO concentrations. The animals had S. pneumoniae (10(5)) injected intracisternally and incubated for 1 hour. Cerebrospinal fluid 200-300 microl was obtained by intracisternal puncture at zero, 2, 4, and 7 hours after drug administration to measure glucose, protein, and lactic acid by standard chemical methods. White blood cell count was measured by hemocytometry. Three groups of five animals were used-control (C), ceftriaxone (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in CSF were obtained by microdialysis and analyzed by high-performance liquid chromatography. Mean (+/- SEM) CSF white blood cell count was significantly higher at 2 hours in the C group than in the other two groups (C 7307 +/- 1302, CTX 605 +/- 345, CTX+D 730 +/- 43/mm3, p<0.002). Ceftriaxone induced a significant rise in protein at 4 hours compared with the other groups (C 364 +/- 107, CTX 1158 +/- 797, CTX+D 365 +/- 100 mg/dl, p<0.02). Cerebrospinal fluid lactic acid was significantly different at 4 and 7 hours between C and CTX+D groups (4-hr C 8.0 +/- 2.2, CTX+D 2.0 +/- 0.4 mmol/L, p<0.05; 7-hr C 10.2 +/- 2.4, CTX+D 2.8 +/- 0.8 mmol/L, p<0.01). Median NO concentrations were significantly elevated in the control group compared with the other two groups (C 11.7, CTX 6.8, CTX+D 6.5 micro, p<0.02 C vs CTX, p<0.01 C vs CTX+D). Average (+/- SEM) NO concentrations were significantly higher in the C group at 4 hours (18.1 +/- 0.4, CTX 5.8 +/- 1.8 microM, p<0.05; CTX+D 11.5 +/- 4.0 microM, p>0.05), whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7 +/- 0.7, C 8.9 +/- 0.4 microM, p=0.055; CTX+D 8.1 +/- 2.2 microM, p<0.05). These results indicate that ceftriaxone with or without dexamethasone significantly decreases lactic acid concentrations and white cell penetration into the CSF in an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone induced a significant elevation in CSF protein. Median NO production in the CSF was significantly attenuated by ceftriaxone.
    Pharmacotherapy 01/1998; 18(3):612-9. · 2.31 Impact Factor
  • P.W. Haney, A.K. Dash
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    ABSTRACT: 5-Aminosalicyclic acid (5-ASA, mesalamine) is an antiinflamatory agent used in the treatment of Crohn's disease and ulcerative colitis. A simple LC method was developed and validated for the analysis of 5-ASA. The chromatographic separation was achieved on a reversed-phase, C8 column with UV detection at 290 nm. This isocratic system was operated at ambient temperature and required 8 min of chromatographic time. The mobile phase consisted of methanol-phosphate buffer pH 7.4 (20:80, v/v). The flow-rate was maintained at 1.0 ml/min. Standard curves were linear over the concentration range of 10 to 200 μg ml−1. Intra-day and inter-day relative standard deviations ranged from 1.1–3.5% and 1.2–4.6% respectively. This method was used to: (1) quantify 5-ASA in pharmaceutical formulations without any complex sample extraction procedure, and (2) study the stability of 5-ASA in Sorensen's phosphate buffer (pH 7.4), Sorensen's phosphate buffer containing 5 mg% (w/v) of Carbopol, and in pharmaceutical formulations.
    Journal of Chromatography A 01/1997; · 4.61 Impact Factor