Self-setting apatite bone cement is consists of metastable calcium phosphates, and was transformed to the low-crystallinity apatite with bioaffinity to natural bones. Various drugs were kneaded in the cements to prepare a drug sustained-release artificial bone cement. Since the in vitro drug release rate from the apatite bone cements followed Higuchi equation, it was possible to control drug release by the parameters, such as drug concentration, porosity, granular diameter and diffusion coefficient. On the other hand, the result of in vitro and in vivo drug release suggested that in vivo drug release from the apatite cement devices was depended on calcium concentration in a body fluid. The results indicated that apatite bone cement containing drugs was transformed into low crystalline apatite with high affinity for bone, so the degree of osteoporosis responsive drug release from artificial bone could be create based on this high functional bone cement. Furthermore, osteoporotic drugs were applied to apatite-collagen composite cement to prepare three-dimensionally perforated macroporous bone cell scaffold. This highly functional artificial bone was shown to be suitable for bone regeneration.
Ischemic stroke is a leading cause of severe disability and death in the world. Tissue plasminogen activator (t-PA) for thrombolytic therapy is the only approved therapeutic agent worldwide for acute ischemic stroke. However, patients received t-PA therapy are extremely limited due to the narrow therapeutic time window (TTW) and the risk of cerebral hemorrhage. In addition, cerebral ischemia/reperfusion (I/R) injury is a serious problem for the patient’s prognosis. Hence, development of more effective therapies has been most desirable. As a distinctive phenomenon after an ischemic stroke, it has been reported that vascular permeability of the blood-brain barrier (BBB) is increased around the ischemic region. Our previous studies revealed that nano-sized liposomes can accumulate in the ischemic region via the disintegrated BBB and that liposomal delivery of neuroprotective agents should be effective for the treatment of cerebral I/R injury. In addition, our recent study demonstrated that combination treatment with liposomal neuroprotectants and t-PA could suppress the deleterious effects of t-PA and prolong its TTW in an ischemic stroke model rat prepared by the photochemically induced thrombosis method. In this review, we introduce our recent findings on ischemic stroke therapy by using liposomal drug delivery systems.
“The hospital formulation” is medicine which hospital pharmacists prepare when doctors cannot provide the medical therapy most suitable for a patient using commercial pharmaceuticals. However, as the responsibilities of pharmacists are increasing, the ability of provide hospital formulations is increasing. The development of evidence-based hospital formulations is thus limited. Especially, the expiration date and storage conditions are very important issue to assure the quality of hospital formulations. In this review, we would like to introduce the retinoic acid gel composed of iota-carrageenan, polyethylene oxide and Emulgen® 408 as an example of the evidence-based hospital formulation. All-trans retinoic acid (RA) gels formulated with various compositions of polyethylene oxide (Emulgen®) and iota-carrageenan (ι-CG) were prepared and their physicochemical properties were evaluated. The compression energy, which is the work required to compress the product through a fixed distance, increased with increasing amount of ι-CG or Emulgen®. The adhesion energy and displacement decreased with increasing amount of ι-CG or Emulgen® due to the progression of gel formation. From the results of the sensory tests, the properties of RA gels such as adhesiveness, gel strength and spreadability seemed to be adjustable depending on the condition of skin by varying the components of RA gels. Through photostability study, the expiration date and storage conditions of RA gels were determined as “4℃ for 28d with no exposure to light.”
Dissolution improvement of poorly water-soluble drugs using solid dispersion has been investigated from the latter part of the twentieth century for the purpose of improved oral drug absorption. However, drug dissolution improvement does not always contribute to the subsequent absorption improvement. Thus, drug dissolution behavior and the dissolved state should be taken into accounts for the formulation study. In this article, effects of pharmaceutical excipients and formulation composition on drug dissolution from solid dispersion are introduced, focusing on drug dissolution behavior from solid dispersion and the dissolved state of drug.
Raman spectroscopy is a spectroscopic technique used to observe vibrational, rotational, and other low-frequency modes in a system. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified. This spectroscopy has the advantage of being able to rapidly and non destructively measure a sample without pretreatment. Application of this method in the pharmaceutical field can qualitatively or quantitatively evaluate active ingredients and additives in drug substance and preparation. It can also be used for evaluation of physical state such as crystal form and degree of crystallinity. In addition, distribution evaluation of active ingredients and additives in the dosage form can be carried out by using a microscopic technique. Further, by using an optical fiber, spectrum measurement can be performed without sampling, for a sample at a place distant from the main body of the device; it is possible to use powerful means for conducting manufacturing process management of pharmaceuticals. In this paper, the fundamental Raman spectra and application examples of formulation evaluation was explained.