| 1. |
- Alhalaweh, Amjad, et al.
(author)
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Effects of polymer and surfactant on the dissolution and transformation profiles of cocrystals in aqueous media
- 2014
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In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 14:2, s. 643-648
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Journal article (peer-reviewed)abstract
- Capturing solubility advantages of cocrystals is of great interest, and thus to understand the mechanism by which different excipients could maintain the supersaturation generated by cocrystals at the course of absorption in aqueous media is essential. To achieve this aim, the impact of different excipients on dissolution behavior of indomethacin-saccharin (IND-SAC) were monitored by measuring the concentrations of cocrystal components in the absence and presence of various concentration of excipients by HPLC, and solid phases were analyzed by differential scanning calorimetry after each experiment and the potential of Raman spectroscopy for monitoring phase transformations in situ was tested. No dissolution advantage was offered by cocrystals in the absence of any solution additive. The polymer and surfactant used in the study increased the solubility of IND but not SAC. This differential solubilization effect is believed to have stabilized the cocrystals for a relevant period for the absorption to take place. This could be attributed to either decreased gap between supersaturation and saturation of the drug or drug interaction with the additives. Understanding the effects of excipients type and concentration on the transformation profile is vital for designing enabling formulations for cocrystals. The eutectic constant may be useful in selecting excipients for stabilizing cocrystals.
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| 2. |
- Alhalaweh, Amjad, et al.
(author)
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Theophylline cocrystals prepared by spray drying : physicochemical properties and aerosolization performance
- 2013
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In: AAPS PharmSciTech. - : Springer Science and Business Media LLC. - 1530-9932. ; 14:1, s. 265-276
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Journal article (peer-reviewed)abstract
- The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC > THF-URE > THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.
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| 3. |
- Ali, Hassan Refat H., et al.
(author)
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Solid-state vibrational spectroscopic investigation of cocrystals and salt of indomethacin
- 2012
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In: CrystEngComm. - 1466-8033. ; 14:20, s. 6665-6674
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Journal article (peer-reviewed)abstract
- Knowledge and control of the solid forms of active pharmaceutical ingredients are important aspects of drug development in the pharmaceutical industry. In this paper, the process of the molecular self-assembly of saccharin cocrystals and the 2-amino-5-methylpyridine salt of indomethacin, in terms of the hydrogen bonding patterns, has been studied in the solid-state using vibrational spectroscopy (Raman and infrared). Interaction patterns in the respective crystalline states were obtained from the single crystal data. The effects of cocrystal and salt formation on the frequencies of the vibrational modes of motion were explained by vibrational spectroscopy and supported by quantum chemical calculations at the density functional theory level, leading to unambiguous assignment of the vibrational spectra of the starting materials and their respective products. Both Raman and infrared spectroscopies were useful, reliable tools for characterizing and distinguishing the indomethacin cocrystals and salt.
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| 4. |
- Ali, Hassan, et al.
(author)
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Vibrational spectroscopic investigation of polymorphs and cocrystals of indomethacin
- 2013
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In: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 39:5, s. 625-634
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Journal article (peer-reviewed)abstract
- Context:Identification of optimal solid form of an active pharmaceutical ingredient and form control are very important in drug development. Thus, the structural information of these forms and in-depth insight on the modes of molecular interactions are necessary, and vibrational spectroscopic methods are well suited for this purpose.Objective:In-depth structural analysis of different solid forms of indomethacin (IND) using Raman and infrared (IR) spectroscopy is the objective. We have investigated the modes of molecular interactions in polymorphs (α and γ), amorphous and discovered cocrystals of IND with nicotinamide (NIC) and trans-cinnamic acid (CIN) coformers.Materials and methods: The solid forms of IND have been prepared; their purity has been verified by differential scanning calorimetry and powder X-ray diffractometry and then studied in the solid-state by Raman and IR spectroscopy. The modes of the interactions were closely investigated from the vibrational data.Results: The key vibrational features of IND solid forms have been specified. The IR (C=O) band at 1713 cm−1 attributed to cyclic acid dimer of γ IND has disappeared in IND–NIC/CIN whilst retained in IND–SAC cocrystal.Discussion:IND cocrystallizes in different conformations and crystal lattices with different coformers. The cyclic acid dimer of IND has been kept on its cocrystallization with saccharin and it could have been broken with NIC and CIN.Conclusions: The complementary nature of Raman and IR spectroscopy allowed unambiguous investigation of the chemical composition of pharmaceutical materials which is of particular importance in the absence of detailed structural information, as in the case of IND–NIC and IND–CIN.
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| 5. |
- Kaialy, Waseem, et al.
(author)
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Effect of carrier particle shape on dry powder inhaler performance
- 2011
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 421:1, s. 12-23
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Journal article (peer-reviewed)abstract
- The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER = 1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER = 4.83 ± 0.18, ECM: ER = 5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a “limit” as increasing carrier ER from 4.83 ± 0.18 (ACM) to 5.89 ± 0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2 = 0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability.
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| 6. |
- Kaialy, Waseem, et al.
(author)
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Influence of lactose carrier particle size on the aerosol performance of budesonide from a dry powder inhaler
- 2012
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In: Powder Technology. - : Elsevier BV. - 0032-5910 .- 1873-328X. ; 227, s. 74-85
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Journal article (peer-reviewed)abstract
- The purpose of this study was to evaluate the effect of carrier particle size on properties of dry powder and its effect on dry powder inhaler (DPI) performance. Commercial α-lactose-monohydrate, a commonly used carrier in DPI formulations, was carefully sieved to obtain different lactose size fractions, namely Lac A (90–125 μm), Lac B (63–90 μm), Lac C (45–63 μm), Lac D (20–45 μm), and Lac E (< 20 μm). The lactose samples were analysed in terms of size, shape, solid state, density, and flowability. Lactose particles were blended with budesonide (< 5 μm) powder to generate five different formulations. These formulations were then evaluated in terms of budesonide-lactose adhesion properties, drug content homogeneity, and in vitro aerosolisation performance. The results demonstrated that lactose samples with smaller particle volume mean diameter have higher amorphous lactose content, higher true density (linear, r2 = 0.9932), higher surface smoothness (linear, r2 = 0.8752), smaller angularity (linear, r2 = 0.921), smaller bulk density, higher porosity (linear, r2 = 0.914), poorer flowability, and higher specific surface area. In general, the smaller the lactose particles the smaller are the budesonide-lactose adhesion properties. Budesonide formulated with smaller lactose particles exhibited smaller aerodynamic diameter and higher amounts of budesonide were delivered to lower stages of the impactor indicating improved DPI aerosolisation performance. However, the use of lactose particles with smaller volume mean diameter had a detrimental effect on budesonide content homogeneity and caused an increase in the amounts of budesonide deposited on oropharyngeal region. Therefore, particle size of the lactose within dry powder inhaler formulations should be selected carefully. Accordingly, higher drug aerosolisation efficiency of lactose particles with smaller size may have to be balanced due to considerations of other disadvantages including poorer flowability, reduced formulation stability, higher potential side effects, and higher dose variability.
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