Novel Oral Drug Formulations

Abstract

The rationale for specialised oral formulations of drugs include prolongation of effect for increased patient convenience and reduction of adverse effects through lowered peak plasma concentrations. Local and systemic adverse effects due to high concentrations of drug can be minimised by the use of controlled release delivery systems. Local effects in the gastrointestinal (GI) tract from the release of irritant drug molecules can also be reduced, but the gastric damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is only partially relieved by formulation approaches because of the involvement of systemic factors in the aetiology of GI adverse events. The advantages for each drug class must be examined. Newer dosage forms include: (i) osmotic pumps and zero order kinetics systems to control the release rate of the drug; (ii) bioadhesive systems and gastric retention devices to control GI transit; (iii) bioerodible hydrogels; (iv) molecular carrier systems (e.g. cyclodextrin-encapsulated drugs) to modulate local toxicity in the GI tract; (v) externally activated systems; and (vi) colloidal systems such as liposomes and microspheres. There is evidence for improved tolerability for a variety of drugs administered in novel delivery systems. However, the evidence for improved tolerability is complicated by the potential bias in adverse reaction reporting systems, and a lack of studies directly comparing conventional and modified release preparations. The technology now available to produce delivery systems which not only release drugs in a controlled and predetermined fashion, but which can also target to regions of the GI tract such as the colon, should allow greater control of therapy and potentially might minimise patient variables. However, the problem of variable GI transit times still eludes solution. Systems which rely on time to release drug might be more vulnerable to patient-to-patient variability than those which respond to local environments. The effect of food intake is more apparent on single-unit, nondisintegrating dosage forms, although of course none so far are immune from influence. The risk of new adverse effects resulting from such positional therapy with novel delivery devices must be considered. Understanding the mechanisms of induction of individual adverse effects can lead to advances in modes of delivery to decrease the potential for adverse reactions and events while maintaining therapeutic efficacy. Increased compliance can led to increased therapeutic control and hence safety. Each system has to be considered on its merits. No generalisations can be made, although invariably the modulation of high peak plasma concentrations diminishes adverse effects due to rapid absorption.

Intramolecular Host–Guest Dynamics of FeCp(CO)2X (X = I and CH3) and Mo2Cp2(CO)6 Included in β‐ or γ‐Cyclodextrin

“…[1,2] A large variety of inorganic and organic "host-guest" molecules have been obtained by using CDs, and their water solubility, low toxicity and relatively low cost make them suitable for a wide range of applications in food technology, [3][4][5] drug delivery systems, [6][7][8][9][10] chemical sensors [11][12][13] and enzyme mimics. [14] Other important applications that have been suggested include enantiomeric enrichment, isomer separation, molecular recognition and removal of undesired compounds from industrial products.…”

“…[15,16] Until recently, studies into the dynamics of CD "hostguest" systems have been greatly limited, as interest has been mainly focused on the characterisation of the crystal structure; however, the ability of the CD cavity to lower the activation energy barriers between molecules in the solid lar motion found within the metal-carbonyl/CD adducts was shown to be dependent on the symmetry, size and orientation of the guest molecule within the host cavity. In the case of Mo 2 Cp 2 (CO) 6 included in γ-CD, the two [MoCp(CO) 3 ] ends of the dimer may be considered as separate dynamic entities: one half of the moiety within the CD cavity exhibits a greater freedom of motion, whereas the other end of the dimer is anchored.…”

“…[17] Moreover, it was shown that the nature and the extent of internal motions are dependent on the interplay between the symmetry and the shape of the host and guest molecules. [18][19][20][21] We previously reported the inclusion of simple binary metal-carbonyl complexes such as Fe(CO) 5 and Cr(CO) 6 in β-and γ-CD cavities and their subsequent dynamics were assessed by using solid-state NMR spectroscopic techniques. [20] Interestingly for the highly symmetric Fe(CO) 5 and Cr(CO) 6 systems, the entire molecule undergoes fast isotropic motion inside the CD.…”

Liberação controlada da eosina impregnada em microesferas de copolímero de quitosana e poli(ácido acrílico)

“…Durante esse período, a indústria farmoquímica se destacou no uso e no aproveitamento de matérias primas de baixo custo e fácil acesso para o desenvolvimento de novos materiais poliméricos, o que permitiu o uso de várias técnicas para encapsulamento de muitos compostos em sistemas de multipartículas, como microesferas e microcápsulas, no intuito de proteger, estabilizar, mascarar os sabores indesejáveis ou modificar as propriedades de liberação [1] . Os sistemas de multipartículas têm suscitado um grande interesse nas formulações orais por apresentarem muitas vantagens, tais como dose única, variabilidade do tempo de trânsito no trato gastrointestinal e a possibilidade de mistura de fármacos de diferentes propriedades de liberação [2,3] . A quitosana (Figura 1), polissacarídeo obtido pela hidrólise alcalina da quitina [4] , age como floculante em tratamentos de efluentes líquidos e como resina quelante na remoção de metais pesados [5][6][7] .…”

A mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poly(vinyl alcohol) for mucosal drug delivery

“…There is a great potential in utilizing these interpolymer complexes in many pharmaceutical preparations, particularly in controlled release drug delivery systems. 2,3 In recent years, drug delivery systems using mucoadhesive drug carriers have gained increasing importance, since they can adhere to the mucosal surfaces of the eye, 4,5 buccal cavity, 6 gastrointestinal tract, 7,8 nasal cavity, 9 and vagina, 10 -12 and thereby increase the therapeutic efficacy. Typical polymers that have been used as mucoadhesive carriers include poly(acrylic acid) (PAA), poly(methacrylic acid), carboxylmethyl cellulose, hydroxypropyl methyl cellulose, and sodium alginate.…”