Using Βeta-cyclodextrin and Plasdone K-30 Polymers for Enhancing Drug Solubility by Spray Drying

Usnig Β-cyclodextrin and Plasdone K-30 Polymers for Enhancing Drug Solubility by Spray Drying

Abstract

The purpose of this study was to investigate improving solubility using hydrophilic/water-soluble polymers as β-Cyclodextrin and Plasdone K-30 in a solid dispersion formulation of Carvedilol a poorly soluble drug. The developed solid dispersion consisted of two components, a drug and a polymer, and the drug was dispersed as amorphous particles in a polymer matrix using the spray drying method. Polymeric solid dispersions were evaluated using solubility tests, in vitro dissolution tests, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and particle size distribution analysis. The study was observed that solid dispersions of each drug showed increase in dissolution rate in comparison and improving drug solubility. However, the beneficial actions require to be verified by adopting various in vivo techniques along with clinical trials for their efficient use as potential remedial moiety.

Introduction

Hypertension remains a significant global health concern, with its management often necessitating the use of antihypertensive drugs. Carvedilol, a widely used beta-blocker, has demonstrated efficacy in hypertension treatment. However, its limited aqueous solubility poses challenges for optimal therapeutic delivery and bioavailability. In recent years, efforts to overcome this limitation have led to the investigation of various solubility enhancement strategies. One promising approach involves the utilization of β-cyclodextrin and Plasdone K-30 polymer as solubility enhancers.¹ β-cyclodextrin, a cyclic oligosaccharide, is known for its ability to form inclusion complexes with hydrophobic molecules, thereby improving their solubility and dissolution rates. Similarly, Plasdone K-30 polymer, a water-soluble polymer, has been shown to enhance drug solubility through mechanisms such as solid dispersion and complexation. ^2–4

In the realm of hypertension therapy, the quest for innovative solutions to enhance the efficacy of antihypertensive drugs has never been more pressing. One promising avenue of research involves the utilization of polymers to improve drug delivery and therapeutic outcomes. Among these polymers, Plasdone K-30 stands out as a versatile and effective candidate for solubility enhancement and formulation optimization.^5–6 Carvedilol is a non-selective beta-blocker and alpha-1 blocker used primarily for the management of hypertension, heart failure, and left ventricular dysfunction following myocardial infarction. It exerts its therapeutic effects by blocking the action of both beta-1 and beta-2 adrenergic receptors, resulting in decreased heart rate, reduced myocardial contractility, and vasodilation. Additionally, its alpha-1 blocking activity contributes to peripheral vasodilation and further lowers blood pressure. This multifaceted pharmacological profile makes carvedilol particularly beneficial for patients with comorbid conditions such as hypertension and heart failure.^7–10 It has been shown to improve symptoms, exercise tolerance, and overall survival in patients with heart failure, making it a cornerstone therapy in the management of this condition. Moreover, carvedilol’s vasodilatory properties help alleviate symptoms of hypertension by reducing systemic vascular resistance and blood pressure.

Several studies have explored the use of β-cyclodextrin^11–13 and Plasdone K-30 polymer to enhance the solubility of poorly water-soluble drugs⁴, including those used in cardiac therapy. These studies have demonstrated promising results in terms of increased drug solubility, dissolution rates, and bioavailability, leading to improved therapeutic outcomes. The purpose of this research is to investigate the potential of β-cyclodextrin and Plasdone K-30 polymer in elevating the solubility of carvedilol, a poorly water-soluble antihypertensive drug.^14–16 By employing advanced solubility enhancement techniques, such as solid dispersion and inclusion complexation, This study builds upon previous research findings and aims to contribute to the development of more effective therapeutic strategies for hypertension treatment.^17–18

There are certain drugs, which have low solubility and need to provide action into body in manner with aim to delay drug release by several hours to treat heart diseases which follows a circadian rhythm. Poor solubility will result in elimination of drug from body without showing therapeutic action. Low solubility becomes limiting step in absorption hence less amount of drug reaches to systemic circulation which is insufficient to produce desired plasma concentration and thereby therapeutic output. Hence there is strong need to explore simple, time-saving method for development of poorly soluble drug to reach desired therapeutic output after oral administration. Thus, present research highlighted developing such polymers using and drug with poor solubility which results in delay in drug release by several hours to treat heart diseases which follows a circadian rhythm with maximizing delivery of drug and attain desired therapeutic effect to nullify the risk of heart attack.

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Material

Carvedilol was obtained as a gift sample from Niksan Pharmaceutical Ltd., Ankleshwar, India. Β-Cyclodextrin was purchased by unique chemicals and Plasdone K-30 was gifted by Lupin Ltd., Pune. All chemicals and solvents used were of pharmaceutical and analytical grade. Double-distilled water was used throughout study for all experimental procedures.

Yuvraj Pandhre, Sandesh Sul, Mahadev Parab et al. Usnig Β-cyclodextrin and Plasdone K-30 Polymers for Enhancing Drug Solubility by Spray Drying, 10 June 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-4465828/v1]

“Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023“

excipients formulation

Using Βeta-cyclodextrin and Plasdone K-30 Polymers for Enhancing Drug Solubility by Spray Drying

Abstract

Introduction

Material

Also read the interesting article:

“Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023“