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Scientist (or higher)

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Scientist (or higher) Position

Solid State Pharma Inc. is a leader in the delivery of crystallization engineering services including screening and selection of polymorphs, co-crystals, salts, and crystallization process development and optimization. SPPI has experienced great success with the workflows that have been developed by combining fundamentals of crystallization and solid form science with years of experience and high throughput techniques. SSPI is conducting research on pharmaceutical crystallization engineering, polymorph screening, salt screening, co-crystal screening, chiral resolution, polymorph quantification, converting amorphous material to crystalline solid, chemical and crystallization process modeling. SSPI is working with a large number of pharmaceutical companies across the globe to help them fully understand the solid state and crystallization of their drug candidates.

About Halifax, Nova Scotia

Halifax is one of the most beautiful and historic Canadian cities. Located on the coast of the Atlantic Ocean, there are numerous parks, campsites, trails and rivers around the city for outdoor activities. City life is also superb. With a population of more than 400,000, Halifax is home to many cultural attractions, museums, art galleries, pubs and clubs. The city hosts three major universities and many community colleges. The beautiful Annapolis valley, which is home to the highest tides in the world, and also mountainous Cape Breton, are within a few hours of drive from Halifax. Halifax has one of the mildest winters in Canada as well as one of the most pleasant summers, which you can enjoy on the beautiful water front boardwalk.

Summary

“Scientist” position is a key contributor to the ongoing research at SSPI reporting to senior scientist or director. “Scientist” will contribute through conducting solid form screening experiments, characterizing the resulting materials, performing crystallization process development for active pharmaceutical ingredients and natural products through utilizing the physical chemistry knowledge and hands on experience. It is expected to have 70-80% lab work.

Job Responsibility

  • Design and perform high throughput polymorph screening, salt screening, solubility measurement and characterization under direction of senior scientist or director
  • Design and perform crystallization process development, under direction of senior scientist or director, to achieve desired polymorph and specifications while meeting the specs
  • Characterize the generated samples using X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermal Gravimetry Analysis (TGA), Liquid Nuclear Magnetic Resonance (NMR), dynamic vapor sorption (DVS), Optical Microscope, Scanning Electron Microscope (SEM), Particle Size Analyzer and HPLC
  • Record all the details of experiments and analytical data
  • Analyze data that are obtained from experiments and draw conclusions
  • Use Deign of Experiment (DOE) software to perform statistical analysis of generated experimental data
  • Write high quality weekly and final reports
  • Routinely present the project results to the team through teleconference
  • Follow the safety rules and housekeeping principles to maintain the working around clean and safe
  • Other responsibilities as assigned

Education & Experience

  • MSc (0-3 years related experience) or PhD (0 year), in chemistry, chemical Engineering or related in the areas of crystallization engineering, physical chemistry, analytical chemistry, solid state characterization or organic chemistry. Previous experience in crystallization science and engineering is a plus.
  • Title will be adjusted for more related experience

 Skills

  • Laboratory techniques for conducting wet chemistry experiments
  • Knowledge of technical report writing is a must
  • Knowledge of XRPD, DSC, TGA, STDA, SEM, DVS, NMR, HPLC and particle size analyzer is a plus
  • Knowledge of crystallization engineering and solid form screening principles is a plus
  • Knowledge of Process Analytical Technologies (PAT) tools is a plus. Specifically, FBRM, React-IR and PVM
  • Knowledge of statistical Design of Experiment (DOE) is a plus
  • Experience with DOE software, e.g. Design Expert is a plus
  • Ability to use Microsoft office software is a must
  • Excellent communication skills and the ability to present the result are required

Visa

Visa sponsorship is not available for this position. Only Canadian citizens, landed immigrants or candidates with valid work permit are encouraged to apply.

Physical Demands

While performing the responsibilities of the job, the employee is required to talk, hear, see, stand, walk, sit, smell and use hands and fingers, to handle or feel. The employee is occasionally required to pick up ordinary weights.

Closing date

Open till filled

Contact information

Please e-mail your CV and cover letter describing why you are an ideal candidate: career@solidstatepharma.com

Stavudine

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Mahmoud Mirmehrabi et. al.
Acta Crystallographica, Section C: Crystal Structure Communications, C61(12), 695-698

Abstract

The crystal structure of the title compound (systematic name: 2′,3′-didehydro-2′,3′-deoxythymidine), C10H12N2O4, consists of two molecules in the asymmetric unit bound together by hydrogen bonds. The conformational geometry differentiates this form of stavudine from its two previously published polymorphs. In addition, a different hydrogen-bonding scheme is observed compared with the previous two structures. This polymorph is the thermodynamically most stable form of the antiviral drug, as evidenced by differential scanning calorimetry (DSC) and IR data.

Characterization of Tautomeric Forms of Ranitidine Hydrochloride: Thermal Analysis, Solid-State NMR, X-ray

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Mahmoud Mirmehrabi, et. al. Journal of Crystal Growth, 260, 517-526

Abstract

The molecular structure of ranitidine hydrochloride (RAN-HCl) has an important influence on the growth of individual crystals and consequently the physical properties such as bulk solid density. This paper suggests that the correct structure of the nitroethenediamine moiety in the Form 2 RAN-HCl is a mixture of enamine and nitronic acid tautomers. Thermal analysis showed that the difference between the two forms Read More

Thermodynamic Modeling of Activity Coefficient and Prediction of Solubility: Part 2. Semi-Predictive or Semi-Empirical Models.

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Mahmoud Mirmehrabi et. al.
Journal of Pharmaceutical Sciences, 95(4), 798-809

Abstract

The solubility of stearic acid, ranitidine hydrochloride, and stavudine were predicted in selected organic solvents. The experimental solubility data of stearic acid and ranitidine hydrochloride were reported in previous work of the authors and stavudine’s solubility was measured in this work. Equilibrium aqueous solubility of crystalline stauvudine was determined at controlled Read More

Thermodynamic Modeling of Activity Coefficient and Prediction of Solubility: Part 1. Predictive Models

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Mahmoud Mirmehrabi et. al.
Journal of Pharmaceutical Sciences, 95(4), 790-797

Abstract

A new activity coefficient model was developed from excess Gibbs free energy in the form G(ex) = cA(a) x(1)(b)…x(n)(b). The constants of the proposed model were considered to be function of solute and solvent dielectric constants, Hildebrand solubility parameters and specific volumes of solute and solvent molecules. The proposed model obeys the Gibbs-Duhem condition for activity coefficient models. To generalize the model and make it as a purely predictive model without any adjustable parameters, its constants were found using the experimental activity coefficient and physical properties of 20 vapor-liquid systems. The predictive capability of the proposed model was tested by calculating the activity coefficients of 41 binary vapor-liquid equilibrium systems and showed good agreement with the experimental data in comparison with two other predictive models, the UNIFAC and Hildebrand models. The only data used for the prediction of activity coefficients, were dielectric constants, Hildebrand solubility parameters, and specific volumes of the solute and solvent molecules. Furthermore, the proposed model was used to predict the activity coefficient of an organic compound, stearic acid, whose physical properties were available in methanol and 2-butanone. The predicted activity coefficient along with the thermal properties of the stearic acid were used to calculate the solubility of stearic acid in these two solvents and resulted in a better agreement with the experimental data compared to the UNIFAC and Hildebrand predictive models.

Solubility, Dissolution Rate and Phase Transition Studies of Ranitidine Hydrochloride Tautomeric Forms

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Mahmoud Mirmehrabi et. al.
International Journal of Pharmaceutics, 282(1-2), 73-85

Abstract

Understanding the polymorphic behavior of pharmaceutical solids during the crystallization process and further in post-processing units is crucial to meet medical and legal requirements. In this study, an analytical technique was developed for determining the composition of two solid forms of ranitidine hydrochloride using two peaks of Fourier transform infrared (FTIR) spectra without the need to grind the samples. Solubility studies of ranitidine hydrochloride showed that Form 2 has a higher solubility than Form 1. Solution-mediated transformation is very slow and occurs from Form 2 to Form 1 and not the reverse. No solid-solid transformation was observed due to grinding or compressing the pure samples of either forms and of a 50/50 wt.% mixture. Grinding was found to be a proper technique for increasing the bulk solid density of the ranitidine hydrochloride without the risk of solid-solid transformation. Dissolution rate found to be equally fast for both forms. The solubility data were modeled using the group contribution parameters and UNIversal QUAsi-Chemical (UNIQUAC) theory. There was a good agreement between the experimental solubility data of ranitidine hydrochloride and the results of UNIQUAC equation.

Improving the Filterability and Solid Density of Ranitidine Hydrochloride Form 1

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Mahmoud Mirmehrabi et. al.
Journal of Pharmaceutical Sciences, 93 (7), 1692-1700

Abstract
Ranitidine hydrochloride Form 1 produced by the original method (Price et al., 1978 US patent) has poor filtration and drying characteristics, which make it less desirable commercially in comparison with Form 2. This article shows that the operating parameters have significant influence on the final properties of Form 1. In terms of filterability and solid bulk density, it was found that at a higher temperature (~48°C), the viscosity of the slurry decreased and improved product quality as compared with operating at room temperature (~25°C). It was found that the rapid addition of acid to the ranitidine base increased product density but led to higher residual solvent inclusion. The presence of excess ranitidine base in the solution and also the manner of reactant addition had a significant influence on the onset of nucleation and the rate of crystallization. The best results in terms of filterability and bulk solid density were obtained using an initial pH of 5.3 and then increasing it to 6.3–6.4 after the onset of nucleation.

Polymorphic Behavior and Crystal Habit of an Anti-Viral/HIV Drug: Stavudine

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Mahmoud Mirmehrabi et. al.
Crystal Growth and Design (American Chemical Society), 6(1), 141-149

Abstract

Different characterization methods (optical microscopy, Karl Ficher titration (KF), XRPD, and solid-state FTIR) were used to identify the two polymorphs and one hydrate of stavudine. The two forms are monotropically related, and form 1 is the stable polymorph. The effects of solvent, impurities, supersaturation, and mixing on the polymorphic occurrence of stavudine are investigated in detail. Hydrogen bonding analysis is employed to qualitatively predict the role of the solvent and structurally related impurities (thymine and thymidine) on polymorphism and crystal habit of stavudine crystals. The impurities showed significant changes in the crystal habit and crystal bulk density of stavudine but had no influence on the polymorphic structure. Depending on the degree of supersaturation at T = 25 °C, a specific polymorph or a mixture of forms 1 and 2 was obtained concomitantly.

An Approach to Solvent Screening for Crystallization of Polymorphic Pharmaceuticals and Fine Chemicals.

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Mahmoud Mirmehrabi and Sohrab Rohani
Journal of Pharmaceutical Sciences, 94 (7), 1560-1576.

Abstract

It is desirable to have a systematic approach for predicting or interpreting the effect of the solvents on the production of polymorphs. A method based on the atomic electronegativity is suggested that calculates the partial charge distribution in the solute and solvent molecules. Using the calculated partial charges, correlations are developed to predict the hydrogen bonding ability of the solute and/or solvent molecules. The predictive capability of the proposed correlations is compared with the results of a quantum mechanics approach. Selection of the right solvent may play a significant role in the formation of a desirable polymorph or solvate. The most important properties of class 2 and 3 solvents of International Conference on Harmonization (ICH) for crystallization of polymorphic compounds are listed in this paper. The partial charge calculation has been used as a tool for analyzing the solvent impact on polymorphic isolation of two compounds: ranitidine hydrochloride (H2 receptor antagonist) and stearic acid (used as excipients or in coating the tablets).