Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral Administration

Box, Karl; Comer, John; Taylor, Robert W.; Karki, Shyam; Ruiz, Rebeca; Price, Robert; Fotaki, Nikoletta

doi:10.1208/s12249-015-0362-5

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…To the best of our knowledge, pharmaceutical cocrystals of zaltoprofen (ZFN) have not been reported to date. [8][9][10][11][12][13][14] ZFN is a nonsteroidal anti-inflammatory propionic acid class drug. It is used in the treatment of acute and chronic inflammation and rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

Superior Solubility and Dissolution of Zaltoprofen via Pharmaceutical Cocrystals

Panzade¹,

Shendarkar²

2019

tjps

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Farmasötik kokristal, zayıf çözünür ilaçların çözünürlüğünü ve çözünmesini arttırmak için umut veren bir araçtır. Zaltoprofen (ZFN) yaygın çözünürlüğe sahip nonsteroid antiinflamatuvar ilaçtır. Bu çalışma, çeşitli koformerlerin taranması yoluyla farmasötik kokteyli aracılığıyla ZFN'nin çözünürlüğünü ve çözünmesini arttırmak için üstlenilmiştir. Gereç ve Yöntemler: Kuru öğütme yöntemi ile 1:1 ve 1:2 oranında ilaç:koformer oranında ZFN kristalleri hazırlanmıştır. Erime noktası ve kristalin fazın çözünürlüğü belirlenmiştir. Potansiyel kristaller differansiyel tarama kalorimetrisi (DSC), kızılötesi spektroskopi ve toz X ışını kırınımı (PXRD) ile karakterize edilmiştir. Kokristaller çözünme hızına ve stabilite çalışmasına tabi tutulmuştur. Bulgular: ZFN-nikotinamid (NIC) kokristal erime noktasında ve çözünürlükte sapma göstermiştir. Kristaller, NIC ile hem 1:1 hem de 1:2 oranında elde edilmiştir. Kızılötesi analizi, ZFN karakteristik bantlarının kaymasını belirgin bir şekilde göstermiştir. Kristallerin kristallenmesi XRPD paterninden belirgin olarak görülmüştür ve 2θ değerindeki yoğun zirvelerdeki kayda değer farklılıklar gözlenmiştir. Kristallerin DSC spektrumları, erime noktasına benzer değiştirilmiş endotermler sergilemiştir. Kristaller, daha hızlı çözünme oranı ve saf ilaçla karşılaştırıldığında çözünme derecesinde % 55 artış göstermiştir. Kristaller, oda sıcaklığında ve hızlandırılmış koşullarda kararlı bulunmuştur. Sonuç: Hazırlanan kristaller, saf ilaca kıyasla daha fazla çözünürlük ve çözünme sergilemiş ve oda sıcaklığında ve hızlandırılmış koşullarda sabit bulunmuştur.

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Section: Introductionmentioning

confidence: 99%

Superior Solubility and Dissolution of Zaltoprofen via Pharmaceutical Cocrystals

Panzade¹,

Shendarkar²

2019

tjps

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“…The cocrystals of piroxicam were reported with different carboxylic acid by solution crystallization, melt crystallization and solvent drop grinding method. 5 - 7 …”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation

Panzade

Shendarkar

Shaikh³

et al. 2017

Adv Pharm Bull

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Purpose: Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers.Methods: Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 32 factorial design.Results: Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate.Conclusion: The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.

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“…The stoichiometric coefficient, n, was selected according to Eq. (14). These estimated results are listed in Table 1.…”

Section: Examples Of Published Solubility-sds Datamentioning

confidence: 99%

“…In the discussion here, n is taken to be k N agg rounded up to the next integral value (using the modulo operator), i.e., n = 1 + k N agg -mod(k N agg , 1) . (14) Note that Eq. (13) is only valid for solubilization of uncharged drugs (e.g., Eq.…”

Section: Molar Solubilization Capacity (K) and The Drug-micelle Bindimentioning

confidence: 99%

Cocrystal solubility-pH and drug solubilization capacity of sodium dodecyl sulfate – mass action model for data analysis and simulation to improve design of experiments

Avdeef¹

2018

ADMET DMPK

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This review discusses the disposition of the anionic surfactant, sodium dodecyl sulfate (SDS; i.e., sodium lauryl sulfate), to solubilize sparingly-soluble drugs above the surfactant critical micelle concentration (CMC), as quantitated by the solubilization capacity (k). A compilation of 101 published SDS k values of mostly poorly-soluble drug molecules was used to develop a prediction model as a function of the drug’s intrinsic solubility, S0, and its calculated H-bond acceptor/donor potential. In almost all cases, the surfactant was found to solubilize the neutral form of the drug. Using the mass action model, the k values were converted to drug-micelle stoichiometric binding constants, Kn, corresponding to drug-micelle equilibria in drug-saturated solutions. An in-depth case study (data from published sources) considered the micellization reactions as a function of pH of a weak base, B, (pKa 3.58, S0 52 μg/mL), where at pH 1 the BH.SDS salt was predicted to precipitate both below and above the CMC. At low SDS concentrations, two drug salts were predicted to co-precipitate: BH.Cl and BH.SDS. Solubility products of both were determined from the analysis of the reported solubility-surfactant data. Above the CMC, in a rare example, the charged form of the drug (BH+) appeared to be strongly solubilized by the surfactant. The constant for that reaction was also determined. At pH 7, the reactions were simpler, as only the neutral form of the drug was solubilized, to a significantly lesser extent than at pH 1. Case studies also featured examples of solubilization of solids in the form of cocrystals. For many cocrystal systems studied in aqueous solution, the anticipated supersaturated state is not long-lasting, as the drug component precipitates to a thermodynamically stable form, thus lowering the amount of the active ingredient available for intestinal absorption. Use of surfactant can prevent this. A recently-described method for predicting the solubility product of cocrystals (coupled with predicted k values described here) allowed for simulations of solubility-pH speciation profiles of cocrystal systems in the presence of SDS. Well in advance of any actual measurements, these simulations can be used to probe conditions favorable to the design of cocrystal experiments where SDS stabilizes cocrystal suspensions against drug precipitation over a predicted range of pH values.

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Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral Administration

Cited by 19 publications

References 25 publications

Superior Solubility and Dissolution of Zaltoprofen via Pharmaceutical Cocrystals

Superior Solubility and Dissolution of Zaltoprofen via Pharmaceutical Cocrystals

Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation

Cocrystal solubility-pH and drug solubilization capacity of sodium dodecyl sulfate – mass action model for data analysis and simulation to improve design of experiments

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