SOLID FORM DEVELOPMENT FOR POORLY SOLUBLE COMPOUNDS

2019 ◽  
pp. 665-687
Author(s):  
Alessandra Mattei ◽  
Shuang Chen ◽  
Jie Chen ◽  
Ahmad Y. Sheikh
Keyword(s):  
Poorly Soluble ◽  
Solid Form ◽  
Form Development

scholarly journals Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts

Crystals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 536
Author(s):  
Xian-Rui Zhang ◽  
Lei Gao ◽  
Gui-Yuan He ◽  
Chao-Jie Chen
Keyword(s):  
Hydrogen Bonds ◽  
Structural Data ◽  
Pharmaceutical Chemistry ◽  
X Ray Diffraction ◽  
Dihydroxybenzoic Acid ◽  
X Ray ◽  
Crystal Contacts ◽  
Poorly Soluble ◽  
Xrd Techniques ◽  
Solid Form

Investigation on the solid-state pharmaceutical chemistry has been known as an intriguing strategy to not only modify the physicochemical properties of drugs but also expand the solid form landscape. Vortioxetine (VOT) is an effective but poorly soluble antidepressant. To improve the solubility of vortioxetine and expand possible solid forms, in this paper, four novel solid forms of vortioxetine with dihydroxybenzoic acids (VOT-23BA, VOT-24BA-TOL, VOT-25BA, and VOT-26BA, 23BA = 2,3-dihydroxybenzoic acid, 24BA = 2,4-dihydroxybenzoic acid, 25BA = 2,5-dihydroxybenzoic acid, 26BA = 2,6-dihydroxybenzoic acid, and TOL = toluene) were synthesized first by a solvent evaporation method and then characterized by single-crystal X-ray diffraction (SCXRD), thermal, and XRD techniques. VOT-24BA-TOL, VOT-25BA, and VOT-26BA, showed similar [2+2] tetrameric R 4 4 (12) hydrogen bonds by acid-piperazine heterosynthon. In the VOT-23BA-H2O salt, the VOT cation and 23BA anion interacted through protonated piperazine-hydroxyl N-H···O hydrogen bonds, not protonated piperazine-deprotonated carboxylic acid N-H···O hydrogen bonds. Solubility studies were carried out in purified water and it was found that the VOT-23BA-H2O, VOT-25BA, and VOT-26BA salts exhibited an increase in water compared to pure VOT. The solubility of the stabilized salt formations followed the order of VOT-25BA > VOT-26BA > VOT-23BA-H2O in purified water.

scholarly journals The potential of computed crystal energy landscapes to aid solid-form development

2016 ◽  
Vol 21 (6) ◽  
pp. 912-923 ◽  
Author(s):  
Sarah L. Price ◽  
Susan M. Reutzel-Edens
Keyword(s):  
Energy Landscapes ◽  
Solid Form ◽  
Form Development

scholarly journals Biorelevant dissolution of candesartan cilexetil

ADMET & DMPK ◽  
2017 ◽  
Vol 5 (1) ◽  
pp. 39 ◽  
Author(s):  
Lucie Gruberová ◽  
Bohumil Kratochvil
Keyword(s):  
Dosage Form ◽  
Candesartan Cilexetil ◽  
Drug Formulation ◽  
Biorelevant Media ◽  
Solid Dosage ◽  
Biorelevant Dissolution ◽  
Dissolution Tests ◽  
Poorly Soluble ◽  
Form Development

<p class="ADMETabstracttext">The choice of an appropriate medium for dissolution tests is an essential step during a dosage form development. The adequate design of dissolution testing enables forecasting in vivo behavior of drug formulation. Biorelevant media were developed for this purpose because dissolution media described in the International Pharmacopoeia are not thoroughly suitable. Therefore, we carried out solubility and dissolution tests in biorelevant media and we compared the results with data measured in compendial dissolution media. A shake-flask method and standard paddle apparatus were used. The concentration was measured by a UV-Vis spectrophotometer. An oral solid dosage form with poorly soluble drug candesartan cilexetil was tested. Significant differences in the solubility and dissolution profiles of candesartan cilexetil were observed. The study offers the overview of compendial and biorelevant media simulating fasted state that can be analyzed by a spectrophotometric technique.</p>

Multicomponent Solid Forms

2018 ◽  
pp. 273-300
Author(s):  
Rahul B. Chavan ◽  
Balvant Yadav ◽  
Anurag Lodagekar ◽  
Nalini R. Shastri
Keyword(s):  
Pharmaceutical Industry ◽  
Scale Up ◽  
Aqueous Solubility ◽  
Multicomponent Systems ◽  
Future Perspectives ◽  
Amorphous System ◽  
Regulatory Guidelines ◽  
Poorly Soluble ◽  
Solid Form ◽  
Widespread Interest

Multicomponent systems provide the option of combining drugs at the supramolecular level. Among these, co-crystals have gained a widespread interest in pharmaceutical industry as US Food and Drug Administration (FDA) recently introduced new regulatory guidelines regarding this solid form that is anticipated to expand patent portfolios. Apart from co-crystals, other multi-component adducts such as co-amorphous system and eutectics are also a topic of interest for pharmaceutical researchers as they provide therapeutic advantages along with improved the aqueous solubility, dissolution, and bioavailability of poorly soluble drugs. This chapter provides a brief overview of multicomponent solid forms, their preparation methodologies, characterization, evaluation, biopharmaceutical aspects, scale up issues, and regulatory perspectives related to these solid forms. In addition, a section on future perspectives that sheds light on new therapeutic hybrids deploying drug-drug and drug-neutraceuticals combinations with improved pharmaceutical and biopharmaceutical attributes is also included.

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

2018 ◽  
Vol 4 (4) ◽  
pp. 523-531
Author(s):  
Hina Mumtaz ◽  
Muhammad Asim Farooq ◽  
Zainab Batool ◽  
Anam Ahsan ◽  
Ashikujaman Syed
Keyword(s):  
Dosage Form ◽  
Pharmaceutical Preparations ◽  
Pharmacokinetic Profile ◽  
In Vitro Dissolution ◽  
Time Saving ◽  
Pharmaceutical Dosage Form ◽  
Short Period ◽  
Form Development

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

Solubility Enhancement of Poorly Soluble Drug Simvastatin by Solid Dispersion Technique

2016 ◽  
Vol 2 (2) ◽  
pp. 91-95
Author(s):  
Neelima Rani T ◽  
Pavani A ◽  
Sobhita Rani P ◽  
Srilakshmi N
Keyword(s):  
Dissolution Rate ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Onset Of Action ◽  
Kneading Method ◽  
Wetting Property ◽  
Poorly Soluble ◽  
Dispersion Technique ◽  
Low Solubility

This study aims to formulate solid dispersions (SDs) of Simvastatin (SIM) to improve the aqueous solubility, dissolution rate and to facilitate faster onset of action. Simvastatin is a BCS class II drug having low solubility & therefore low oral bioavailability. In the present study, SDs of simvastatin different drug-carrier ratios were prepared by kneading method. The results showed that simvastatin solubility & dissolution rate enhanced with polymer SSG in the ratio 1:7 due to increase in wetting property or possibly may be due to change in crystallinity of the drug.

Choice of diagnosis of solid form of papillary carcinoma in pathological investigation rather than fine needle aspiration

2020 ◽  
Author(s):  
Lali Tigishvili ◽  
Keti Tsomaia ◽  
Khatuna Khachapuridze ◽  
Nino Kekelidze ◽  
Giorgi Mchedlishvili ◽  
...  
Keyword(s):  
Papillary Carcinoma ◽  
Fine Needle Aspiration ◽  
Needle Aspiration ◽  
Fine Needle ◽  
Solid Form

Technological Advancements in Oral Films

2019 ◽  
Vol 9 (01) ◽  
pp. 15-20
Author(s):  
B Pandey ◽  
A B Khan
Keyword(s):  
3D Printing ◽  
Historical Background ◽  
Poorly Soluble Drugs ◽  
Modern Approach ◽  
Poorly Soluble ◽  
Critical Process Parameters ◽  
Biopharmaceutical Properties ◽  
Oral Films ◽  
Hot Melt ◽  
Modern Technologies

The aim of the review was to explore the necessity, advantages and different techniques of oral films for enhancing solubility of poorly soluble drugs with an emphasis on the newer, state-of the art technologies, such as 3D printing and hot-melt extrusion (HME). The historical background of oral films is presented along with the regularly used techniques. The modern approach of quality-by-design (QbD) is unravelled, identifying appropriate critical process parameters (CPP) and applied to oral films. A section is devoted modern technologies such as 3D printing and HME of oral films. Oral films are innovative formulations by which poorly soluble drugs have been founds to give positive results in enhancing their solubility and dissolution characteristics. With modern sophisticated techniques, precise mass production of oral films has been given a thrust. Oral films have better patient compliance, improved biopharmaceutical properties, improved efficacy, and better safety. By applying QbD and implementation of modern technologies the newer generation of oral films are yielding promising results

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