-
Journal of Controlled Release :... Dec 2015In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response of... (Review)
Review
In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response of drug products. Since the U.S. Food and Drug Administration (FDA) published a regulatory guidance on the development, evaluation, and applications of IVIVC for extended release (ER) oral dosage forms in 1997, IVIVC has been one of the most important issues in the field of pharmaceutics. However, even with the aid of the FDA IVIVC Guidance, only very limited Abbreviated New Drug Application (ANDA) submission for ER oral drug products included adequate IVIVC data to enable the completion of bioequivalence (BE) review within first review cycle. Establishing an IVIVC for non-oral dosage forms has remained extremely challenging due to their complex nature and the lack of in vitro release methods that are capable of mimicking in vivo drug release conditions. This review presents a general overview of recent advances in the development of IVIVC for complex non-oral dosage forms (such as parenteral polymeric microspheres/implants, and transdermal formulations), and briefly summarizes the knowledge gained over the past two decades. Lastly this review discusses possible directions for future development of IVIVC for complex non-oral dosage forms.
Topics: Animals; Delayed-Action Preparations; Dosage Forms; Drug Administration Routes; Humans; In Vitro Techniques; Pharmaceutical Preparations
PubMed: 26419305
DOI: 10.1016/j.jconrel.2015.09.052 -
Drug Design, Development and Therapy 2024Oral administration of dosage forms is convenient and beneficial in several respects. Lipid nanoparticulate dosage forms have emerged as a useful carrier system in... (Review)
Review
Oral administration of dosage forms is convenient and beneficial in several respects. Lipid nanoparticulate dosage forms have emerged as a useful carrier system in deploying low solubility drugs systemically, particularly class II, III, and IV drugs of the Biopharmaceutics Classification System. Like other nanoparticulate delivery systems, their low size-to-volume ratio facilitates uptake by phagocytosis. Lipid nanoparticles also provide scope for high drug loading and extended-release capability, ensuring diminished systemic side effects and improved pharmacokinetics. However, rapid gastrointestinal (GI) clearance of particulate delivery systems impedes efficient uptake across the mucosa. Mucoadhesion of dosage forms to the GI mucosa results in longer transit times due to interactions between the former and mucus. Delayed transit times facilitate transfer of the dosage form across the mucosa. In this regard, a balance between mucoadhesion and mucopenetration guarantees optimal systemic transfer. Furthermore, the interplay between GI anatomy and physiology is key to ensuring efficient systemic uptake. This review captures salient anatomical and physiological features of the GI tract and how these can be exploited for maximal systemic delivery of lipid nanoparticles. Materials used to impart mucoadhesion and examples of successful mucoadhesive lipid nanoformulations are highlighted in this review.
Topics: Nanoparticles; Liposomes; Gastrointestinal Tract; Administration, Oral; Lipids; Drug Delivery Systems
PubMed: 38476206
DOI: 10.2147/DDDT.S439975 -
PloS One 2022There are many paediatric specific challenges such as lack of age-appropriate dosage forms, inability of young children to swallow tablets and capsules and poor...
BACKGROUND
There are many paediatric specific challenges such as lack of age-appropriate dosage forms, inability of young children to swallow tablets and capsules and poor acceptability, during administration of oral dosage forms of medications to children. Parents adopt various methods which they consider best to circumvent this problem. The objective of this study was to describe the administration practice by parents when giving oral dosage forms of medications to children.
METHODS
A descriptive cross-sectional study was conducted to assess the administration practice of 1800 oral dosage forms of medications administered to children under the age of 12 years using validated indicators. A pre-tested interviewer-administered questionnaire given to parents or caregivers was used to collect the necessary data. The data were analysed using descriptive statistics.
RESULTS
Data from 1800 oral dosage forms was obtained from 663 children. Of the 1287 solid dosage forms, almost one-third were manipulated by parents at the time of giving the medications to children. They were crushed and dissolved in water given to children. In about 17% of instances safety of water was questionable. In 92% of instances, measuring device was found to be inappropriate.
CONCLUSION
Administration of oral dosage forms of medications to children is far from ideal and hinders successful use of medications in children.
Topics: Child; Humans; Child, Preschool; Cross-Sectional Studies; Resource-Limited Settings; Administration, Oral; Tablets; Capsules; Dosage Forms
PubMed: 36548310
DOI: 10.1371/journal.pone.0276379 -
European Journal of Pharmaceutical... Oct 2017The knowledge and experiences obtained with oral phospholipid excipients is increasing continuously. Nevertheless the present number of oral products using these... (Review)
Review
The knowledge and experiences obtained with oral phospholipid excipients is increasing continuously. Nevertheless the present number of oral products using these excipients as essential excipient is very limited. This is remarkable to note, since phospholipids play a significant role in the food uptake mechanisms of the GI tract and these mechanisms could be translated into suitable dosage forms and corresponding drug delivery strategies. In addition, phospholipid excipients are multifunctional biodegradable, non-toxic excipients, which can be used in oral dosage forms as wetting agents, emulsifier, solubilizer and matrix forming excipients. Especially natural phospholipid excipients, made from renewable sources, may be considered as environmentally friendly excipients and as a viable alternative to synthetic phospholipid and non-phospholipid analogues. This review describes 1) essential physico-chemical properties of oral phospholipid excipients 2) the fate of orally administered phospholipids with respect to absorption and metabolism in the GI tract 3) the main dosage forms used for oral administration containing phospholipids. These elements are critically assessed and areas of future research of interest for the use of oral phospholipid excipients are summarized.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Excipients; Humans; Micelles; Molecular Structure; Phospholipids; Solubility; Structure-Activity Relationship
PubMed: 28711714
DOI: 10.1016/j.ejps.2017.07.008 -
The AAPS Journal Dec 2012Metrics are discussed which are used for the evaluation of bioequivalence of modified-release formulations. In order to ensure the therapeutic equivalence of the... (Review)
Review
Metrics are discussed which are used for the evaluation of bioequivalence of modified-release formulations. In order to ensure the therapeutic equivalence of the compared drug products, it would be important to contrast measures which are additional to area under the curve (AUC) and C (max). For delayed-release products, the assessment of lag times is informative. For extended-release dosage forms, comparisons of the half-value duration and the midpoint duration time are useful. For some modified-release formulations with complicated, multiphasic concentration profiles, the comparison of partial AUCs is important. In determinations of the bioequivalence of extended-release dosage forms, investigations performed under steady-state conditions rather than after single dosing can yield enhanced probability of therapeutic equivalence, especially with substantial accumulation of the drug products. In steady-state investigations of bioequivalence, evaluation of the trough concentration and of the peak trough fluctuation is informative.
Topics: Area Under Curve; Delayed-Action Preparations; Humans; Pharmaceutical Preparations; Pharmacokinetics; Therapeutic Equivalency; Time Factors
PubMed: 22910857
DOI: 10.1208/s12248-012-9396-8 -
Chemical & Pharmaceutical Bulletin 2011The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important... (Review)
Review
The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.
Topics: Animals; Dosage Forms; Humans; Nanoparticles; Pharmaceutical Preparations; Technology, Pharmaceutical; X-Ray Diffraction
PubMed: 21297291
DOI: 10.1248/cpb.59.147 -
Therapeutic Delivery Aug 2017Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user... (Review)
Review
Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.
Topics: Anti-HIV Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Suppositories
PubMed: 28825395
DOI: 10.4155/tde-2017-0056 -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2013Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of... (Review)
Review
Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of liquisolid systems (LSS) is a novel technique for improving solubility, dissolution and bioavailability of such drugs. The basic principle of LSS preparation is conversion of the drug in liquid state into a free-flowing, compressible, dry powder through its absorption into suitable excipients - porous carriers (aluminometasilicates, microcrystalline cellulose), subsequently coated with material having high absorption capacity (silicon dioxide commonly known as colloidal silica). LSS exhibit advantages such as lower production costs compared to soft capsules, simple processing and enhanced drug release. The main benefit is higher bioavailability of the liquid drug, caused by a large surface area available for absorption. The article tries to clarify specific aspects connected with the formulation of LSS: properties of excipients (surface area, absorption capacity), variables related to the processing (solubility, liquid load factor) and dosage form evaluation.
Topics: Biological Availability; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; Excipients; Humans; Pharmaceutical Preparations; Porosity; Powders; Solubility
PubMed: 24451071
DOI: 10.2478/acph-2013-0034 -
AAPS PharmSciTech 2008Practical examples of preformulation support of the form selected for formulation development are provided using several drug substances (DSs). The examples include... (Review)
Review
Practical examples of preformulation support of the form selected for formulation development are provided using several drug substances (DSs). The examples include determination of the solubilities vs. pH particularly for the range pH 1 to 8 because of its relationship to gastrointestinal (GI) conditions and dissolution method development. The advantages of equilibrium solubility and trial solubility methods are described. The equilibrium method is related to detecting polymorphism and the trial solubility method, to simplifying difficult solubility problems. An example of two polymorphs existing in mixtures of DS is presented in which one of the forms is very unstable. Accelerating stability studies are used in conjunction with HPLC and quantitative X-ray powder diffraction (QXRD) to demonstrate the differences in chemical and polymorphic stabilities. The results from two model excipient compatibility methods are compared to determine which has better predictive accuracy for room temperature stability. A DSC (calorimetric) method and an isothermal stress with quantitative analysis (ISQA) method that simulates wet granulation conditions were compared using a 2 year room temperature sample set as reference. An example of a pH stability profile for understanding stability and extrapolating stability to other environments is provided. The pH-stability of omeprazole and lansoprazole, which are extremely unstable in acidic and even mildly acidic conditions, are related to the formulation of delayed release dosage forms and the resolution of the problem associated with free carboxyl groups from the enteric coating polymers reacting with the DSs. Dissolution method requirements for CR dosage forms are discussed. The applicability of a modified disintegration time (DT) apparatus for supporting CR dosage form development of a pH sensitive DS at a specific pH such as duodenal pH 5.6 is related. This method is applicable for DSs such as peptides, proteins, enzymes and natural products where physical observation can be used in place of a difficult to perform analytical method, saving resources and providing rapid preformulation support.
Topics: Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Crystallography, X-Ray; Delayed-Action Preparations; Drug Stability; Excipients; Hydrogen-Ion Concentration; Powder Diffraction; Solubility; Technology, Pharmaceutical; Temperature; Time Factors
PubMed: 18431656
DOI: 10.1208/s12249-008-9067-3 -
The AAPS Journal Mar 2009Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings... (Review)
Review
Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.
Topics: Administration, Intravaginal; Anti-HIV Agents; Body Fluids; Contraceptive Devices, Female; Drug Delivery Systems; Female; HIV Infections; Humans; Hydrogels; Nanoparticles; Ointments; Tablets; Vagina
PubMed: 19194802
DOI: 10.1208/s12248-009-9082-7