A New Approach for β-Cyclodextrin Conjugated Drug Delivery System in Cancer Therapy

: Natural cyclodextrins (CDs) are macrocyclic starch molecules discovered a decade ago, in which α-, β-, and γ-CD were commonly used. They originally acted as pharmaceutical excipients to enhance the aqueous solubility and alter the physicochemical properties of drugs that fall under class II and IV categories according to the Biopharmaceutics Classification System (BPS). The industrial significance of CDs became apparent during the 1970s as scientists started to discover more of CD’s potential in chemical modifications and the formation of inclusion complexes. CDs can help in masking and prolonging the half-life of drugs used in cancer. Multiple optimization techniques were discovered to prepare the derivatives of CDs and increase their complexation and drug delivery efficiency. In recent years, due to the advancement of nanotechnology in pharmaceutical sectors, there has been growing interest in CDs. This review mainly focuses on the formulation of cyclodextrin conjugated nanocarriers using graphenes, carbon nanotubes, nanosponges, hydrogels, dendrimers, and polymers to achieve drug-release characteristics specific to cells. These approaches benefit the discovery of novel anti-cancer treatments, solubilization of new drug compounds, and cell specific drug delivery properties. Due to these unique properties of CDs, they are essential in achieving and enhancing tumor-specific cancer treatment.

DISSOLUTION IMPROVEMENT OF KETOPROFEN THROUGH POLYMER MATRIX COMPOSITE POVIDONE K-30/TiO2

Ketoprofen is a nonsteroidal anti-inflammatory drug that has been classified into Class II as per the Biopharmaceutics Classification System. This substance has low solubility i.e. only 51 mg/L at 22℃. Therefore, a study of ketoprofen modification prepared in Polymer Matrix Composite (PMC) using Povidone K-30, coated with TiO2 as an effort to improve its dissolution profile, had been conducted. Composite particles were prepared through a dissolving method with a ratio of ketoprofen: Povidone K30 i.e. 1: 1 (F1), 1: 2 (F2), and 1: 4 (F3). They were evaluated and continued on the coating process using TiO2 30%, 40%, and 50%. Results of the study revealed that the PMC provides an absence of chemical intervention against ketoprofen. All the used combination ratios improved the dissolution profile by using phosphate buffer media pH 7.5 for 60 minutes. After coating, a release profile was obtained by running it on phosphate buffer media at pH 6.8 for 8 hours, this showing a sustained release profile.

METHODS FOR IMPROVING ALPHA-MANGOSTIN SOLUBILITY: A REVIEW

Solubility is an important parameter to achieve for the bioavailability of a drug to reach the therapeutic windows. Garcinia mangostana Linn is a plant with great potency for the development of natural medicine. Alpha-mangostin is one of the secondary metabolites of G. mangostana and has been reported to have several pharmacological activities. The Biopharmaceutics Classification System (BCS) is a system that classifies drugs based on their solubility and permeability. Due to its low solubility but high permeation, alpha-mangostin is categorized into class II of the Biopharmaceutics Classification System. Therefore, the determination of dosage forms and modification of solubility enhancers is limited due to its physical properties, as mentioned above. This disadvantage requires new methods to improve its solubility to administer alpha-mangostin, especially for oral administration. Here, we discuss the development of the methods to increase alpha-mangostin solubility to be applied to formulate a dosage form to reach a useful plasma level for medication.

Cocrystal formation of loratadine-succinic acid and its improved solubility

Objectives Loratadine belongs to Class II compound of biopharmaceutics classification system (BCS) due its low solubility and high membrane permeability. Cocrystal is a system of multicomponent crystalline that mostly employed to improve solubility. Succinic acid is one of common coformer in cocrystal modification. This research aims to investigate cocrystal formation between loratadine and succinic acid and its effect on solubility property of loratadine. Methods Cocrystal of loratadine-succinic acid was prepared by solution method using methanol as the solvent. Cocrystal formation was identified under observation of polarization microscope and analysis of the binary phase diagram. The cocrystal phase was characterized by differential thermal analysis (DTA), powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Solubility study was conducted in phosphate-citrate buffer pH 7.0 ± 0.5 at 30 ± 0.5 °C. Results Loratadine is known to form cocrystal with succinic acid in 1:1 M ratio. Cocrystal phase has lower melting point at 110.9 °C. Powder diffractograms exhibited new diffraction peaks at 2θ of 5.28, 10.09, 12.06, 15.74, 21.89, and 28.59° for cocrystal phase. IR spectra showed that there was a shift in C=O and O–H vibration, indicating intermolecular hydrogen bond between loratadine and succinic acid. SEM microphotographs showed different morphology for cocrystal phase. Loratadine solubility in cocrystal phase was increased up to 2-fold compared to loratadine alone. Conclusions Cocrystal of loratadine and succinic acid is formed by stoichiometry of 1:1 via C=O and H–O interaction. Cocrystal phase shows different physicochemical properties and responding to those properties, it shows improved loratadine solubility as well.

Overview on Biopharmaceutics Classification System (BCS) based biowaiver requirements in African countries

Biopharmaceutics Classification System (BCS)-based biowaiver are meant to reduce the need for establishing in vivo bioequivalence in situations where in vitro data may be considered to provide a reasonable estimate of the relative in vivo performance of two products. The BCS is a scientific approach designed to predict medicinal absorption based on the aqueous solubility and intestinal absorptive characteristics of the Pharmaceutical product. To ensure interchangeability, the multisource product must be therapeutically equivalent to the comparator product. Types of in vivo equivalence studies include comparative pharmacokinetic studies, comparative pharmacodynamic studies and comparative clinical studies. This article briefly explains the BCS based biowaiver requirements in six major African countries i.e. Zimbabwe, South Africa, Uganda, Kenya, Botswana and Tanzania which facilitates regulatory medicine approval process when the dossier (application) is approved based on evidence of equivalence other than In vivo studies.

Review: Effect of Different Methods on the Multicomponents Crystal Formation from Medicinal Natural Ingredient Compounds

Solubility is an important parameter for the bioavailability of drugs that are difficult to dissolve. Natural compounds that are included in class II in the Biopharmaceutics Classification System (BCS) are Apigenin, Quercetin, Genistein, Curcumin, and Piperin. These drugs have low solubility in water and high permeability so that they affect the dissolution rate and as well as their bioavailability, to increase the solubility they are made with multicomponent crystals. This review aims to provide information on the method of making crystal multicomponent to increase the solubility and dissolution rate of BCS II drugs. Several methods that can be used in multicomponent are solvent drop grinding, solvent evaporation, assisted grinding, and slurry. The results showed that multicomponent crystals using several methods could increase the solubility and dissolution rates.

ICH Guideline for Biopharmaceutics Classification System-Based Biowaiver (M9): Toward Harmonization in Latin American Countries

The biopharmaceutical classification system (BCS) is a very important tool to replace the traditional in vivo bioequivalence studies with in vitro dissolution assays during multisource product development. This paper compares the most recent harmonized guideline for biowaivers based on the biopharmaceutics classification system and the BCS regulatory guidelines in Latin America and analyzes the current BCS regulatory requirements and the perspective of the harmonization in the region to develop safe and effective multisource products. Differences and similarities between the official and publicly available BCS guidelines of several Latin American regulatory authorities and the new ICH harmonization guideline were identified and compared. Only Chile, Brazil, Colombia, and Argentina have a more comprehensive BCS guideline, which includes solubility, permeability, and dissolution requirements. Although their regulatory documents have many similarities with the ICH guidelines, there are still major differences in their interpretation and application. This situation is an obstacle to the successful development of safe and effective multisource products in the Latin American region, not only to improve their access to patients at a reasonable cost, but also to develop BCS biowaiver studies that fulfill the quality standards of regulators in developed and emerging markets.

NIOSOMES AS AN APPROACH TO IMPROVE THE SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS II DRUGS

Based on their solubility and permeability, drugs are typically divided into four classes (Classes I–IV) according to the biopharmaceutics classification system (BCS). Of these classes, BCS class II drugs have high permeability and low solubility; not only do these characteristics constitute the rate-limiting step in the formulation of these drugs but the low solubility in water results in low bioavailability. Thus, methods for improving their solubility have been developed using lipid carriers such as liposomes, niosomes, and aquasomes; other approaches include self-micro-emulsifying drug delivery systems (SMEDDS) and self-nano-emulsifying drug delivery systems (SNEDDS). Currently, niosome-based drug delivery systems that utilize nonionic surfactants, drugs, and cholesterol in varying ratios are being widely used to deliver both hydrophilic and lipophilic drugs in addition to several other applications of niosomes.

Co-Amorphous Formulations of Furosemide with Arginine and P-Glycoprotein Inhibitor Drugs

In this study, the amino acid arginine (ARG) and P-glycoprotein (P-gp) inhibitors verapamil hydrochloride (VER), piperine (PIP) and quercetin (QRT) were used as co-formers for co-amorphous mixtures of a Biopharmaceutics classification system (BCS) class IV drug, furosemide (FUR). FUR mixtures with VER, PIP and QRT were prepared by solvent evaporation, and mixtures with ARG were prepared by spray drying in 1:1 and 1:2 molar ratios. The solid-state properties of the mixtures were characterized with X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) in stability studies under different storage conditions. Simultaneous dissolution/permeation studies were conducted in side-by-side diffusion cells with a PAMPA (parallel artificial membrane permeability assay) membrane as a permeation barrier. It was observed with XRPD that ARG, VER and PIP formed co-amorphous mixtures with FUR at both molar ratios. DSC and FTIR revealed single glass transition values for the mixtures (except for FUR:VER 1:2), with the formation of intermolecular interactions between the components, especially salt formation between FUR and ARG. The co-amorphous mixtures were found to be stable for at least two months under an elevated temperature/humidity, except FUR:ARG 1:2, which was sensitive to humidity. The dissolution/permeation studies showed that only the co-amorphous FUR:ARG mixtures were able to enhance both the dissolution and permeation of FUR. Thus, it is concluded that formulating co-amorphous salts with ARG may be a promising option for poorly soluble/permeable FUR.

Novel Solid Forms of Insomnia Drug Suvorexant with Improved Solubility and Dissolution: Accessing Salts from Salt-Solvates Route

Suvorexant (SRX) is a dual orexin receptor antagonist used for the treatment of insomnia. It belongs to the Biopharmaceutics Classification System (BCS) class-II with high permeability and poor solubility in...