Studies on paracetamol crystals produced by growth in aqueous solutions

Femi-Oyewo, Mbang N.; Spring, M. S.

doi:10.1016/0378-5173(94)90257-7

Cited by 56 publications

(46 citation statements)

References 15 publications

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“…[33][34][35] In another study, it has been shown that the crystallization of paracetamol from water in the presence of gelatin or PVP, changed the crystal habit of paracetamol and caused a decrease in crystal yield. 36,37 The reduction in the yield of the agglomerates made in the presence of stabilizer could be due to the influence of stabilizer on drug solubility. Greater drug solubility in the presence of stabilizer (Table 2), may result in incomplete solvate of the initial crystals, leading to a reduction in the yield for agglomerates.…”

Section: Yieldmentioning

confidence: 99%

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Maghsoodi

Nokhodchi

2016

Adv Pharm Bull

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Section: Yieldmentioning

confidence: 99%

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Maghsoodi

Nokhodchi

2016

Adv Pharm Bull

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“…9 The list of polymers tested is extensive and includes both hydrophilic and hydrophobic powders, such as ethylcellulose, methylcellulose (CM), polyethylene glycol (PEG), polyvinyl alcohol (PVA), agar, gelatine, polyvinyl pyrrolidone (PVP), poly(ethylene oxide) (PEO), corn starch, carrageenan, polyethylene (PE), polyvinyl chloride (PVC), polymethyl methacrylate (PMMA) and hydroxylpropyl methylcellulose (HPMC) to name a few. 3,[8][9][10][11][12] Generally, crystallisation additives are effective in producing polymorphs of pharmaceuticals while avoiding others by encouraging the growth of a desirable form or disrupting the growth of the other form. 8,9,13,14 Modification of crystal shape occurs as the polymer deposition on the crystal surface inhibits the growth of specific surfaces of the crystal.…”

Section: Introductionmentioning

confidence: 99%

“…Stagnant crystallisation experiments have shown that polymers and other additives can help driving the production of a given polymorph, [6][7][8][9] reducing the crystal size 10 or controlling the crystal shape. 9 The list of polymers tested is extensive and includes both hydrophilic and hydrophobic powders, such as ethylcellulose, methylcellulose (CM), polyethylene glycol (PEG), polyvinyl alcohol (PVA), agar, gelatine, polyvinyl pyrrolidone (PVP), poly(ethylene oxide) (PEO), corn starch, carrageenan, polyethylene (PE), polyvinyl chloride (PVC), polymethyl methacrylate (PMMA) and hydroxylpropyl methylcellulose (HPMC) to name a few.…”

Section: Introductionmentioning

confidence: 99%

Hydroxypropyl Methylcellulose as a Novel Tool for Isothermal Solution Crystallization of Micronized Paracetamol

Reis

Liu

Reis

et al. 2014

Crystal Growth & Design

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Pulmonary inhalation is increasingly being selected as a preferred route for the delivery of both small and large drug macromolecules for the treatment of a range of pathologies. The direct crystallization of micronized powders, in particular, paracetamol, remains difficult, as it requires the ability to work in high solution supersaturations where agglomeration, wall crusting, and heterogeneous nucleation hinder the control of crystal size and crystal size distribution. Polymer additives are recognized to help drive the production of a given polymorph or controlling crystal shape by means of adsorption on the crystal surface. With the aim of exploiting the polymer-control nucleation and growth of crystals for enhanced direct crystallization of micronized powders, batch cooling crystallization of paracetamol in water was carried out in the presence of 0.1−0.8% w/w hydroxypropyl methylcellulose (HPMC). In the presence of polymer, the onset of nucleation was delayed and extended beyond the cooling time of the solution, resulting in an isothermal cooling crystallization and the production of micronized paracetamol with a mean crystal size D 50 , in the range of 15−20 μm and an improved crystal size distribution. Equally, the rate generation of solution cloudiness was reduced by over 3-fold for the highest HPMC concentration tested, with no detectable impact on final product yield. The mechanisms for nucleation delay and growth inhibition by HPMC is unknown; however, a modification of crystal's shape observed upon the addition of HPMC to the solution suggested it might be related to mass transfer limitations and intermolecular hydrogen bonding between the large HPMC and the small drug molecules. This technique can potentially be used for direct crystallization of other micronized drugs.

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“…Compared to the control experiment, the steady state and hence the level of supersaturation is quite high, confirming the effect of HPMC on growth and nucleation suppression. 21,59 Furthermore, there was a dramatic reduction in the process yield compared to the no additive experiment. Due to the dramatic effect of 0.05 wt % HPMC on the delay and suppression of PCM nucleation and growth rate, further investigations were conducted at lower concentrations (0.001 and 0.003 wt %).…”

Section: Resultsmentioning

confidence: 99%

“…The polymer hydroxyl propyl methyl cellulose (HPMC) was identified as a possible candidate. In their study, Femi-Oyewo et al 21 investigated the effect of additives on the crystallization of PCM from aqueous solution and in particular on the crystal structure and processability of PCM raw material in the final solid dosage form. HPMC was found to significantly suppress nucleation and growth of PCM in the concentration range 0.1− 0.7 wt %, resulting in very fine crystals.…”

Section: Introductionmentioning

confidence: 99%

Monitoring Continuous Crystallization of Paracetamol in the Presence of an Additive Using an Integrated PAT Array and Multivariate Methods

Powell

Saleemi²,

Rielly

et al. 2016

Org. Process Res. Dev.

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In this study, an automated intelligent decision support (IDS) framework was applied to monitor the continuous crystallization of form I paracetamol (PCM) and determine steady-state operation. A modified single-stage mixed suspension mixed product removal (MSMPR) crystallizer was used to investigate methods to minimize early onset of fouling and encrustation by carrying out crystallizations in the presence and absence of hydroxyl propyl methyl cellulose (HPMC) additive. The effectiveness of HPMC toward controlling the crystallization process and alleviating fouling and encrustation for prolonged operation of the MSMPR was investigated over a range of concentrations. HPMC was found to suppress nucleation and growth, thereby controlling the crystallization and alleviating fouling and encrustation over extended operating periods. HPMC also affected the product crystal morphology, leading to predominantly tabular shaped crystals. Steady state in the MSMPR was characterized using the IDS, which consisted of an integrated and ancillary array of process analytical technologies (PAT), including the application of Raman spectroscopy with multivariate calibration for solution phase concentration measurement.

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Studies on paracetamol crystals produced by growth in aqueous solutions

Cited by 56 publications

References 15 publications

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

Hydroxypropyl Methylcellulose as a Novel Tool for Isothermal Solution Crystallization of Micronized Paracetamol

Monitoring Continuous Crystallization of Paracetamol in the Presence of an Additive Using an Integrated PAT Array and Multivariate Methods

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