Raj Suryanarayanan

University of Minnesota Duluth, Duluth, Minnesota, United States

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Publications (117)399.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Physical instability of amorphous solid dispersions can be a major impediment to their widespread use. We characterized the molecular mobility in amorphous solid dispersions of itraconazole (ITZ) with each polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) with the goal of investigating the correlation between molecular mobility and physical stability. Dielectric spectra showed two mobility modes: α-relaxation at temperatures above the glass transition temperature (Tg) and β-relaxation in the sub-Tg range. HPMCAS substantially increased the α-relaxation time, with an attendant increase in crystallization onset time and a decrease in crystallization rate constant, demonstrating the correlation between α-relaxation and stability. The inhibitory effect on α-relaxation as well as stability was temperature dependent and diminished as the temperature was increased above Tg. PVP, on the other hand, affected neither the α-relaxation time nor the crystallization onset time, further establishing the link between α-relaxation and crystallization onset in solid dispersions. However, it inhibited the crystallization rate, an effect attributed to factors other than mobility. Interestingly, both of the polymers acted as plasticizers of β-relaxation, ruling out the latter's involvement in physical stability.
    Molecular Pharmaceutics 10/2014; · 4.57 Impact Factor
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    ABSTRACT: The objectives of this study were to measure the apparent surface acidity of common excipients and to correlate the acidity with the chemical stability of an acid-sensitive active pharmaceutical ingredient (API) in binary API-excipient powder mixtures. The acidity of 26 solid excipients was determined by two methods, (i) by measuring the pH of their suspensions or solutions and (ii) the pH equivalent (pHeq) measured via ionization of probe molecules deposited on the surface of the excipients. The chemical stability of an API, atorvastatin calcium (AC), in mixtures with the excipients was evaluated by monitoring the appearance of an acid-induced degradant, atorvastatin lactone, under accelerated storage conditions. The extent of lactone formation in AC-excipient mixtures was presented as a function of either solution/suspension pH or pHeq. No lactone formation was observed in mixtures with excipients having pHeq > 6, while the lactone levels were pronounced (> 0.6% after 6 weeks at 50°C/20% RH) with excipients exhibiting pHeq < 3. The three pHeq regions (> 6, 3-6, and < 3) were consistent with the reported solution pH-stability profile of AC. In contrast to the pHeq scale, lactone formation did not show any clear trend when plotted as a function of the suspension/solution pH. Two mechanisms to explain the discrepancy between the suspension/solution pH and the chemical stability data were discussed. Acidic excipients, which are expected to be incompatible with an acid-sensitive API, were identified based on pHeq measurements. The incompatibility prediction was confirmed in the chemical stability tests using AC as an example of an acid-sensitive API.
    AAPS PharmSciTech 10/2014; · 1.58 Impact Factor
  • Khushboo Kothari, Vishard Ragoonanan, Raj Suryanarayanan
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    ABSTRACT: We investigated the correlation between molecular mobility and physical stability in three model systems, including griseofulvin, nifedipine, and nifedipine-polyvinylpyrrolidone dispersion, and identified the specific mobility mode responsible for instability. The molecular mobility in the glassy as well as the supercooled liquid states of the model systems were comprehensively characterized using dynamic dielectric spectroscopy. Crystallization kinetics was monitored by powder X-ray diffractometry using either a laboratory (in the supercooled state) or a synchrotron (glassy) X-ray source. Structural (α-) relaxation appeared to be the mobility responsible for the observed physical instability at temperatures above Tg. Although the direct measurement of the structural relaxation time below Tg was not experimentally feasible, dielectric measurements in the supercooled state were used to provide an estimate of the α-relaxation times as a function of temperature in glassy pharmaceuticals. Again, there was a strong correlation between the α-relaxation and physical instability (crystallization) in the glassy state but not with any secondary relaxations. These results suggest that structural relaxation is a major contributor to physical instability both above and below Tg in these model systems.
    Molecular Pharmaceutics 08/2014; · 4.57 Impact Factor
  • Khushboo Kothari, Vishard Ragoonanan, Raj Suryanarayanan
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    ABSTRACT: In dielectric spectroscopy, a technique traditionally used to characterize molecular mobility in polymers, the sample is usually analyzed as a thin film. In recent years, the technique has been extended to characterize both drug substances and drug products and has revealed a correlation between molecular mobility and stability. However, for pharmaceutical systems, analysis of powders is strongly preferred over films. Therefore, the dielectric behavior of several compounds of pharmaceutical interest—nifedipine, indomethacin, itraconazole, and griseofulvin—obtained using powder and film samples were compared. The magnitudes of the intrinsic dielectric properties were affected by the sample configuration with the powder samples consistently yielding lower values. The use of effective medium theories enabled us to account for the effect of air in the powder samples. The relaxation time, a property of immense importance to the pharmaceutical community, was not influenced by the sample configuration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci
    Journal of Pharmaceutical Sciences 08/2014; · 3.13 Impact Factor
  • Prakash Sundaramurthi, Raj Suryanarayanan
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    ABSTRACT: According to label claims, in commercial solid dosage forms, azithromycin (AZI) exists either as a monohydrate (MH) or as a dihydrate (DH). Although these two forms are known to be relatively stable in the solid state, AZI sesquihydrate (SH) was observed in a drug product. This was believed to be a consequence of a processing-induced phase transformation. Our goal was to prepare and characterize AZI SH and map its solid-state transition pathways with other AZI phases. When dehydrated at temperatures <80°C, DH yielded an isomorphic dehydrate, whereas dehydration at ≥80°C yielded SH. Heating SH to 100°C or holding at 0% RH at room temperature, yielded an amorphous product through an intermediate isomorphic dehydrate, isostructural to SH. On the other hand, dehydration of MH (at ≥60°C) resulted in amorphization with no intermediate crystalline anhydrate. Diagnostic XRD peaks of AH, MH, SH, and DH enabled their unambiguous identification. However, the presence of crystalline excipients hindered active pharmaceutical ingredient characterization in drug product. Pattern subtraction method was used to selectively remove the contribution of the crystalline excipients to the overall diffraction pattern, thereby facilitating the physical characterization of AZI in the drug product. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci
    Journal of Pharmaceutical Sciences 08/2014; · 3.13 Impact Factor
  • Sisir Bhattacharya, Sunny P Bhardwaj, Raj Suryanarayanan
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    ABSTRACT: To determine the effect of annealing on the two secondary relaxations in amorphous sucrose and in sucrose solid dispersions. Sucrose was co-lyophilized with either PVP or sorbitol, annealed for different time periods and analyzed by dielectric spectroscopy. In an earlier investigation, we had documented the effect of PVP and sorbitol on the primary and the two secondary relaxations in amorphous sucrose solid dispersions (1). Here we investigated the effect of annealing on local motions, both in amorphous sucrose and in the dispersions. The average relaxation time of the local motion (irrespective of origin) in sucrose, decreased upon annealing. However, the heterogeneity in relaxation time distribution as well as the dielectric strength decreased only for β1- (the slower relaxation) but not for β2-relaxations. The effect of annealing on β2-relaxation times was neutralized by sorbitol while PVP negated the effect of annealing on both β1- and β2-relaxations. An increase in local mobility of sucrose brought about by annealing could be negated with an additive.
    Pharmaceutical Research 05/2014; · 4.74 Impact Factor
  • Vishard Ragoonanan, Raj Suryanarayanan
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    ABSTRACT: We hypothesize that ultrasonication can accelerate solute crystallization in freeze-concentrates. Our objective is to demonstrate ultrasonication as a potential predictive tool for evaluating physical stability of excipients in frozen solutions. The crystallization tendencies of lyoprotectants (trehalose, sucrose), carboxylic acid buffers (citric, tartaric, malic, and acetic) and an amino acid buffer (histidine HCl) were studied. Aqueous solutions of buffers, lyoprotectants and mixtures of the two were cooled from room temperature to -20°C and sonicated to induce solute crystallization. The crystallized phases were identified by X-ray diffractometry (laboratory or synchrotron source). Sonication accelerated crystallization of trehalose dihydrate in frozen trehalose solutions. Sonication also enhanced solute crystallization in tartaric (200 mM; pH 5), citric (200 mM pH 4) and malic (200 mM; pH 4) acid buffers. At lower buffer concentrations, longer annealing times following sonication were required to facilitate solute crystallization. The time for crystallization of histidine HCl progressively increased as a function of sucrose concentration. The insonation period required to effect crystallization also increased with sucrose concentration. Sonication can substantially accelerate solute crystallization in the freeze-concentrate. Ultrasonication may be useful in assessing the crystallization tendency of formulation constituents used in long term frozen storage and freeze-drying.
    Pharmaceutical Research 01/2014; · 4.74 Impact Factor
  • Naveen K Thakral, Vishard Ragoonanan, Raj Suryanarayanan
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    ABSTRACT: Model tablet formulations containing thiamine hydrochloride [as a nonstoichiometric hydrate (NSH)] and dicalcium phosphate dihydrate (DCPD) were prepared. In intact tablets, the water released by dehydration of DCPD mediated the transition of NSH to thiamine hydrochloride hemihydrate (HH). The use of an X-ray microdiffractometer with an area detector enabled us to rapidly and simultaneously monitor both the phase transformations. The spatial information, gained by monitoring the tablet from the surface to the core (depth profiling), revealed that both DCPD dehydration and HH formation progressed from the surface to the tablet core as a function of storage time. Film coating of the tablets with ethyl cellulose caused a decrease in both the reaction rates. There was a pronounced lag time, but once initiated, the transformations occurred simultaneously throughout the tablet. Thus the difference in the phase transformation behavior between the uncoated and the coated tablets could not have been discerned without the depth profiling. Incorporation of hydrophilic colloidal silica as a formulation component further slowed down the transformations. By acting as a water scavenger it maintained a very "dry" environment in the tablet matrix. Finally, by coating the NSH particles with hydrophobic colloidal silica, the formation of HH was further substantially decelerated. The microdiffractometric technique not only enabled direct analyses of tablets but also provided the critical spatial information. This helped in the selection of excipients with appropriate functionality to prevent the in situ phase transformations.
    Molecular Pharmaceutics 07/2013; · 4.57 Impact Factor
  • A Saxena, Y C Jean, R Suryanarayanan
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    ABSTRACT: Our objective is to compare the physical properties of materials obtained from two different methods of annealing reversal, that is, water sorption-desorption (WSD) and heating above glass transition temperature (HAT). Trehalose was annealed by storing at 100 °C for 120 h. The annealing effect was reversed either by WSD or HAT, and the resulting materials were characterized by differential scanning calorimetry (DSC), water sorption studies, and positron annihilation spectroscopy (PAS). While the products obtained by the two methods of annealing reversal appeared to be identical by conventional characterization methods, they exhibited pronounced differences in their water sorption behavior. Positron annihilation spectroscopy (PAS), by measuring the fractional free volume changes in the processed samples, provided a mechanistic explanation for the differences in the observed behavior.
    Molecular Pharmaceutics 07/2013; · 4.57 Impact Factor
  • Mehak Mehta, Sunny P Bhardwaj, Raj Suryanarayanan
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    ABSTRACT: A potential drawback with the use of mannitol as a bulking agent is its existence as mannitol hemihydrate (MHH; C6H14O6(.)0.5H2O) in the lyophile. Once formed during freeze-drying, MHH dehydration may require secondary drying under aggressive conditions which can be detrimental to the stability of thermolabile components. If MHH is retained in the lyophile, the water released by MHH dehydration during storage has the potential to cause product instability. We systematically identified the conditions under which anhydrous mannitol and MHH crystallized in frozen systems with the goal of preventing MHH formation during freeze-drying. When mannitol solutions were cooled, the temperature of solute crystallization was the determinant of the physical form of mannitol. Based on low temperature X-ray diffractometry (using both laboratory and synchrotron sources), MHH formation was observed when solute crystallization occurred at temperatures ⩽ -20 °C while anhydrous mannitol crystallized at temperatures ⩾ -10 °C. The transition temperature (anhydrate - MHH) appears to be ∼ -15 °C. The use of a freeze-dryer with controlled ice nucleation technology enabled anhydrous mannitol crystallization at ∼ -5 °C. Thus, ice crystallization followed by annealing at temperatures ⩾ -10 °C can be an effective strategy to prevent MHH formation.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 04/2013; · 3.15 Impact Factor
  • Kapildev K Arora, Seema Thakral, Raj Suryanarayanan
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    ABSTRACT: PURPOSE: To demonstrate two sequential solid-state reactions in intact tablets: dehydration of active pharmaceutical ingredient (API), and cocrystal formation between the anhydrous API and a second formulation component mediated by the released water. To evaluate the implication of this in situ phase transformation on the tablet dissolution behavior. METHODS: Tablets containing theophylline monohydrate (TPM) and anhydrous citric acid (CA) were stored at 40°C in sealed polyester pouches and the relative humidity in the headspace above the tablet was continuously measured. Dehydration to anhydrous theophylline (TPA) and the product appearance (TPA-CA cocrystal) were simultaneously monitored by powder X-ray diffractometry. Carbamazepine dihydrate and nicotinamide formed the second model system. RESULTS: The water of crystallization released by TPM dehydration was followed first by deliquescence of citric acid, evident from the headspace relative humidity (~ 68%; 40°C), and then the formation of TPA-CA cocrystal in intact tablets. The noncovalent synthesis resulted in a pronounced decrease in the dissolution rate of theophylline from the tablets. Similarly, the water released by dehydration of carbamazepine dihydrate caused the cocrystallization reaction between anhydrous carbamazepine and nicotinamide. CONCLUSIONS: The water released by API dehydration mediated cocrystal formation in intact tablets and affected dissolution behavior.
    Pharmaceutical Research 04/2013; · 4.74 Impact Factor
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    ABSTRACT: The goal was to investigate the correlation between molecular mobility and physical stability and identify the specific mobility mode responsible for instability. The molecular mobility of amorphous itraconazole, in the glassy as well as the supercooled liquid state, was comprehensively characterized using dynamic dielectric spectroscopy. Isothermal frequency sweeps in the 5 - 40 °C temperature range revealed a β-relaxation which exhibited Arrhenius temperature dependence. As the temperature approached Tg, β-relaxation became progressively less resolved due to interference from the high frequency tail of the alpha-relaxation and then transformed into an excess wing. Above Tg, non-linear temperature dependence of the alpha-relaxation was described by the Vogel-Tammann-Fulcher (VTF) model. Itraconazole was found to be a fragile glass former with a VTF strength parameter of ~ 4. Isothermal crystallization kinetics, at several temperatures over the range of 75 to 95 °C, was best described by the 3-dimensional nucleation and growth model. Primary relaxation appeared to be the mobility responsible for the observed physical instability at temperatures above Tg as indicated by the linear correlation of alpha-relaxation with both crystallization onset and kinetics (represented by the inverse of the crystallization rate constant). A strong coupling between global mobility and crystallization onset was evident. However, for growth kinetics, the coupling was less pronounced, indicating the involvement of factors other than global mobility.
    Molecular Pharmaceutics 12/2012; · 4.57 Impact Factor
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    ABSTRACT: Solid-state NMR spectroscopy (SSNMR), coupled with powder X-ray diffraction (PXRD), was used to identify the physical forms of gabapentin in samples prepared by recrystallization, spray drying, dehydration, and milling. Four different crystalline forms of gabapentin were observed: form I, a monohydrate, form II, the most stable at ambient conditions, form III, produced by either recrystallization or milling, and an isomorphous desolvate produced from desolvating the monohydrate. As-received gabapentin (form II) was ball-milled for 45 min in both the presence and absence of hydroxypropylcellulose (HPC). The samples were then stored for 2 days at 50°C under 0% relative humidity and analyzed by (13)C SSNMR and PXRD. High-performance liquid chromatography was run on the samples to determine the amount of degradation product formed before and after storage. The (1)H T (1) values measured for the sample varied from 130 s for the as-received unstressed material without HPC to 11 s for the material that had been ball-milled in the presence of HPC. Samples with longer (1)H T (1) values were substantially more stable than samples that had shorter T (1) values. Samples milled with HPC had detectable form III crystals as well. These results suggest that SSNMR can be used to predict gabapentin stability in formulated products.
    AAPS PharmSciTech 11/2012; · 1.58 Impact Factor
  • Sunny P Bhardwaj, Raj Suryanarayanan
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    ABSTRACT: PURPOSE: The work aims at investigating the correlation of water sorption potential with different measures of molecular mobility in an annealed amorphous model compound (trehalose). METHODS: Amorphous trehalose, prepared by freeze-drying, was annealed at 100°C (17°C < T (g)) for up to 120 h. Global molecular mobility was studied using a broadband dielectric spectrometer in the frequency range of 10(6)-10(-2) Hz. Enthalpic recovery was measured by differential scanning calorimetry and water sorption profiles were obtained using an automated vapor sorption balance. RESULTS: As a function of annealing time, there was an increase, both in average α-relaxation time and enthalpic recovery and a decrease in the amount of sorbed water. A strong linear correlation was observed between the water sorption potential and the dielectric relaxation time, indicating a common underlying mechanism of the effect of annealing time on these properties. Enthalpic recovery, which is widely used as a measure of structural relaxation, did not correlate well with the extent of water sorption. CONCLUSIONS: The α-relaxation time can be used as a predictor of the water sorption potential of amorphous trehalose. It will be of interest and value to develop such predictive models for other amorphous compounds of pharmaceutical interest.
    Pharmaceutical Research 10/2012; · 4.74 Impact Factor
  • Sunny P. Bhardwaj, Raj Suryanarayanan
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    ABSTRACT: Amorphous trehalose was prepared by different methods, viz., freeze-drying, spray-drying and dehydration of trehalose dihydrate. The different molecular relaxations were characterized by dynamic dielectric spectroscopy. The preparation method significantly affected the structural relaxation time and its temperature dependence in the glassy region. The order of activation energy for α-relaxation was spray-dried > freeze-dried > dehydrated. However, the secondary relaxation times remained essentially unaffected by the preparation method. Isothermal crystallization kinetics was studied at several temperatures above the glass transition temperature (Tg). A linear correlation was observed between the crystallization time (inverse of crystallization rate constant) and the average α-relaxation time, suggesting a similar molecular origin for these two processes. There was also strong coupling of the crystallization onset time with global molecular mobility in the supercooled liquid region, enabling the development of predictive models. The observed experimental onset times were in excellent agreement with the predicted values at temperatures around and below Tg.
    Molecular Pharmaceutics 10/2012; 9(11):3209–3217. · 4.57 Impact Factor
  • Sunny P Bhardwaj, Raj Suryanarayanan
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    ABSTRACT: Dielectric spectroscopy was used to comprehensively characterize the molecular mobility in amorphous trehalose, an extensively used bioprotective agent. Isothermal frequency sweeps were carried out at different temperatures in the glassy and supercooled liquid states of freeze-dried trehalose. Two previously reported secondary relaxations were observed at temperatures far below its glass transition temperature (T(g)). At temperatures close to T(g), removal of dc conductivity contribution revealed a relaxation peak. The origin of this peak was evaluated using several diagnostic tests and determined to be the α-relaxation. There was also an excess wing in the high-frequency tail of α-relaxation. Sub-T(g) annealing caused the primary relaxation to shift to lower frequencies, enabling resolution of the excess wing, which was characterized to be the true Johari-Goldstein (JG) relaxation. A qualitatively similar effect of annealing on JG relaxation was also observed. The average relaxation times of the two previously reported secondary relaxations were unaffected by annealing.
    The Journal of Physical Chemistry B 08/2012; 116(38):11728-36. · 3.61 Impact Factor
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    ABSTRACT: The purpose of this study was to perform physical characterization of pentamidine isethionate (PI) in frozen and freeze-dried systems and to monitor the phase behavior during all the stages of freeze-drying. Frozen aqueous PI solutions as well as the final lyophiles were characterized by differential scanning calorimetry and X-ray diffractometry. The effect of cosolutes, cosolvents, and processing conditions on the PI crystallization behavior during freeze-drying was evaluated. In frozen aqueous solutions, irrespective of the cooling rate and the initial solute concentration, PI readily crystallized as a trihydrate (C(19) H(24) N(4) O(2) ·3H(2) O). It dehydrated to a poorly crystalline anhydrate upon drying at 100 mTorr. The presence of a readily crystallizing cosolute or an organic cosolvent did not influence the physical form of PI in the final lyophile. On the contrary, even in the absence of cosolutes and cosolvents, the crystalline trihydrate was retained when the chamber pressure was increased to 500 mTorr. By altering the drying conditions, it was possible to obtain either a crystalline trihydrate or a poorly crystalline anhydrate. The stability of PI is dependent on its physical form and only the amorphous PI undergoes discoloration. The PI stability can be enhanced by retaining it in a crystalline state in the lyophile.
    Journal of Pharmaceutical Sciences 01/2012; 101(5):1732-43. · 3.13 Impact Factor
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    ABSTRACT: The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior.
    Journal of Pharmaceutical Sciences 12/2011; 101(4):1410-22. · 3.13 Impact Factor
  • Prakash Sundaramurthi, Raj Suryanarayanan
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    ABSTRACT: Lyophilization is a commonly used drying technique for thermolabile pharmaceuticals. Crystallization of formulation components may occur during various stages of the freeze-drying process. In frozen solutions, while crystallization of bulking agents is desirable, both from processing and product-elegance perspectives, buffer salt crystallization can cause a significant pH shift. Lyoprotectants (compounds that protect macromolecules, both during freeze-drying and subsequent storage) are effective only when retained amorphous. This review presents numerous applications of differential scanning calorimetry to characterize pharmaceutical systems in frozen state. These studies are aimed at defining the processing parameters and optimizing the freeze-drying cycle. Low temperature pH measurement and sub-ambient X-ray diffractometry served as excellent complementary tools in the characterization of frozen systems. The phase behavior of the systems during annealing (of frozen solutions), primary and secondary drying were monitored by X-ray diffractometry. Finally, the interplay of formulation composition and processing parameters on the development and optimization of freeze-drying cycles are reviewed.
    Advanced drug delivery reviews 12/2011; 64(5):384-95. · 11.96 Impact Factor
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    ABSTRACT: Gabapentin is known to undergo intramolecular cyclization to form a lactam (gaba-l) with concomitant loss of water. Gabapentin was milled in a planetary mill for 15–60 min. Unmilled and milled gabapentin were stored at 50°C with relative humidity ranged between 5% and 90%. The unmilled and milled samples were assayed for gabapentin and gaba-l by reversed phase-high-performance liquid chromatography and also subjected to powder X-ray diffraction, solid-state nuclear magnetic resonance and surface area analyses. The rates of lactamization in the milled gabapentin samples correlated to increased surface area, milling duration, and in-process lactam levels. This effect of milling could not be explained solely by the increase in surface area with increased milling time but was more likely due to increased regions of crystal disorder caused by the mechanical and thermal milling stresses. The lactamization rate of milled gabapentin samples was greatest in the presence of the lowest humidity conditions and dramatically decreased with increasing humidity. In particular, milled gabapentin appeared to be much more stable at humidity levels greater than 31% RH. This finding could not be attributed to the possibility of lactam hydrolysis at high humidity but rather to a competitive annealing process wherein milling-induced crystal defects were lost upon exposure to atmospheric moisture thereby stabilizing the milling-damaged drug substance.
    AAPS PharmSciTech 09/2011; · 1.58 Impact Factor

Publication Stats

1k Citations
399.66 Total Impact Points


  • 1990–2014
    • University of Minnesota Duluth
      • College of Pharmacy
      Duluth, Minnesota, United States
  • 1990–2012
    • University of Minnesota Twin Cities
      • • Department of Pharmaceutics
      • • College of Pharmacy
      Minneapolis, MN, United States
  • 2009
    • Kent State University
      • Department of Physics
      Kent, Ohio, United States
  • 2002
    • Creighton University
      • Department of Pharmacy Sciences
      Omaha, NE, United States