Compaction of Pharmaceuticals

MRS Bulletin ◽  
1997 ◽  
Vol 22 (12) ◽  
pp. 34-37 ◽  
Author(s):  
Nicholas G. Lordi ◽  
Alberto M. Cuitino
Keyword(s):  
Oral Administration ◽  
High Speed ◽  
Extended Release ◽  
Oral Absorption ◽  
Dosage Forms ◽  
Over The Counter ◽  
First Choice ◽  
Market Requirements ◽  
Low Volume ◽  
Aseptic Conditions

It has been estimated that more than 80% of all medication doses are administered as tablets—that is, in unit dosage forms prepared by compacting powders in dies. For drugs with acceptable oral-absorption profiles, the compacted tablet is the first choice as a delivery system in drug development. Modern tablets range in size from 25 milligrams (veterinary implants) to several grams (veterinary “boluses”). The most common tablet shape is the double convex-faced disk. Shapes range from capsule to triangular forms, in many instances with bisects embossed or debossed with identification codes and company logos. Tablets may be either film- or sugar-coated, may be designed for immediate or extended release, or may be prepared as multilayer or laminated forms. In addition to oral administration, tablets may be predissolved or designed to be disintegrated in the mouth, or may be administered by injection or as suppositories. Production rates for over-the-counter products such as acetaminophen tablets can exceed three 1,000-kg batches per week, requiring high-speed multiple-station tablet presses for production. In contrast, implants—which have low-volume market requirements—must be made under aseptic conditions on special singlestation presses.

Oral absorption of propiverine solution and of the immediate and extended release dosage forms: influence of regioselective intestinal elimination

2008 ◽  
Vol 64 (11) ◽  
pp. 1085-1092 ◽  
Author(s):  
Karen May ◽  
Thomas Giessmann ◽  
Danilo Wegner ◽  
Reinhard Oertel ◽  
Christiane Modess ◽  
...  
Keyword(s):  
Extended Release ◽  
Oral Absorption ◽  
Dosage Forms ◽  
Intestinal Elimination

scholarly journals Gliclazide: Biopharmaceutics Characteristics to Discuss the Biowaiver of Immediate and Extended Release Tablets

2020 ◽  
Vol 10 (20) ◽  
pp. 7131
Author(s):  
Bruna de Carvalho Mapa ◽  
Lorena Ulhôa Araújo ◽  
Neila Márcia Silva-Barcellos ◽  
Tamires Guedes Caldeira ◽  
Jacqueline Souza
Keyword(s):  
Extended Release ◽  
Immediate Release ◽  
Pharmacokinetic Profile ◽  
Dosage Forms ◽  
New Drugs ◽  
Essential Medicines ◽  
World Health ◽  
Drug Candidate ◽  
Dissolution Profile ◽  
First Choice

The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.

The Length of Disulfide Bond-Containing Linkages Impacts the Oral Absorption and Antitumor Activity of Paclitaxel Prodrugs-Loaded Nanoemulsions

Nanoscale ◽  
2021 ◽  
Author(s):  
Yanlin Gao ◽  
Shiyi Zuo ◽  
Lingxiao Li ◽  
Tian Liu ◽  
Fudan Dong ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Oral Administration ◽  
Disulfide Bond ◽  
Rational Design ◽  
Oral Absorption ◽  
Oral Paclitaxel

Rational design of oral paclitaxel (PTX) preparations is still a challenge. Many studies focus on developing PTX-loaded nanoemulsions (NEs) for oral administration. Unfortunately, PTX has poor affinity with the commonly...

scholarly journals A STUDY ON DIFFERENT PELLET FORMATION TECHNIQUES AND ITS EVALUATION PARAMETERS-A REVIEW

2019 ◽  
pp. 7-13
Author(s):  
REHANA BEGUM A. ◽  
GANESH N. S. ◽  
VINEETH CHANDY
Keyword(s):  
Oral Administration ◽  
Particle Production ◽  
Dosage Forms ◽  
Review Article ◽  
Spheroidal Particle ◽  
Safety And Efficacy ◽  
Pellet Production ◽  
Pellet Formation ◽  
Evaluation Parameters ◽  
Extrusion Spheronization

This review article deals with the various pelletization techniques utilized in the pharmaceutical industry for spheroidal particle production i.e., pellet for mainly oral administration which can be further formulated into several other dosage forms such as tablets, capsules or can be administered as such. Now-a-days oral administration has become the most versatile, convenient and common route of drug administration which ultimately focuses on patient compliance. The technique which is setting horizon in pelletization is “Extrusion Spheronization” because of its simple and easy steps involved in pellet production in a faster way. This review also includes the characterization and evaluation of pellets to ensure its quality, safety and efficacy to give out the required therapeutic activity after administration.

Lack of influence of the antidopaminergic drug domperidone on basal and TRH-stimulated TSH-serum levels after oral administration

1982 ◽  
Vol 101 (4) ◽  
pp. 550-554 ◽  
Author(s):  
K. W. Wenzel ◽  
J. Döring
Keyword(s):  
Oral Administration ◽  
Thyroid Function ◽  
Oral Absorption ◽  
Statistical Significance ◽  
Oral Intake ◽  
Serum Levels ◽  
The Novel ◽  
Antiemetic Drug ◽  
First Pass ◽  
The Difference

Abstract. Since antidopaminergic drugs are known to elevate basal and TRH-stimulated TSH-serum levels and since this effect was also shown after iv administration of the novel dopamine antagonistic agent domperidone, it was investigated, whether this antiemetic drug could interfere after oral intake with the evaluation of thyroid function. Oral domperidone caused a marked TSH-enhancement of TRH-induced TSH increments in 6 out of 14 euthyroid subjects, with no statistical significance, however. The difference between oral and parenteral influence as well as inter-individual changes are probably due to the varying first pass effect of the drug after oral absorption.

Abstract 1696: Compound RVX-208 Modulates HDL-C Levels and Function in Non-human Primates and in Early (phase I) Human Trials

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Larbi Krimbou ◽  
Ravi Jahagirdar ◽  
Dana Bailey ◽  
Anouar Hafiane ◽  
Isabelle Ruel ◽  
...  
Keyword(s):  
Oral Administration ◽  
Healthy Volunteers ◽  
Size Distribution ◽  
Cholesterol Efflux ◽  
Oral Absorption ◽  
Therapeutic Potential ◽  
Human Study ◽  
Treated Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Hdl Function

The novel compound RVX-208 is a small molecule that upregulates the gene expression of apoA-I and raises HDL-C in non-human primates. Here, we examined the effects of oral administration of RVX-208 on serum apoA-I and HDL-C levels , HDL size distribution, and HDL function. African green monkeys received RVX-208 (7.5, 15 and 30 mg/kg; twice daily and 60 mg/kg; once daily) or vehicle control for 28, 42, and 63 days. We report that RVX-208 chronic treatment resulted in a highly significant increase in the average of serum apoA-I and HDL-C levels (57% and 92%, respectively). Interestingly, RVX-208 treatment modified the distribution of HDL particle size causing a significant increase in preβ1-LpA-I and larger α1-LpA-I species. The ability of serum to promote cholesterol efflux via ABCA1, ABCG1 or SR-BI-dependent pathways in a cell culture model was significantly increased by RVX-208. The phase Ia safety and pharmacokinetic human study comprised of a total of 80 subjects. In the multiple ascending dose arm, 24 participants were randomly assigned to 3 cohorts of 8 healthy volunteers (6 active and 2 placebo), and received oral administration of RVX-208 at 2, 3 and 8 mg/kg per day or placebo for 7 days. The compound was well tolerated and had good oral absorption meeting the objectives of safety and pharmacokinetics. ApoA-I, HDL-C, HDL size distribution and ABCA1-dependent cholesterol efflux were assessed at days 1 (predose) and 7. The percent change from baseline to day 7 for apoA-I was 11% higher (P = 0.03) in the RVX-208 treated participants compared to placebo. Interestingly, preβ1-LpA-I change was 30% (P = 0.02) higher in the actively treated group and was found to strongly correlate with increased apoA-I levels (R2 = 0.72). Furthermore, ABCA1-dependent cholesterol efflux change was 10% higher (P = 0.03) and was found to correlate with increased preβ1-LpA-I . Taken together, these pharmacodynamic data from human healthy volunteers show consistent trends in apoA-I production and HDL functionality, supporting the findings in the African green monkey. Further investigation of the effect of RVX-208 on the HDL metabolic pathway is ongoing in humans and animals to establish the mechanisms of action and therapeutic potential in treating atherosclerotic cardiovascular disease.

scholarly journals Case Series about the Changed Antiplatelet Protocol for Carotid Endarterectomy in a Teaching Hospital: More Patients with Complications?

2018 ◽  
Vol 04 (04) ◽  
pp. e220-e225
Author(s):  
Martijn Marsman ◽  
Denise Özdemir- van Brunschot ◽  
Abdelkarime Jahrome ◽  
Nic Veeger ◽  
Wouter Schuiling ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Carotid Endarterectomy ◽  
Extended Release ◽  
Case Series ◽  
Daily Practice ◽  
Postoperative Hemorrhage ◽  
Consecutive Series ◽  
Cerebrovascular Event ◽  
First Choice ◽  
Ischemic Complications

Introduction In the Netherlands, clopidogrel monotherapy increasingly replaces acetylsalicylic acid and extended release dipyridamole as the first-choice antiplatelet therapy after ischemic stroke. It is unknown whether the risk of peri- and postoperative hemorrhage in carotid artery surgery is higher in patients using clopidogrel monotherapy compared with acetylsalicylic acid and extended release dipyridamole. We therefore retrospectively compared occurrence of perioperative major and (clinical relevant) minor bleedings during and after carotid endarterectomy of two groups using different types of platelet aggregation inhibition after changing our daily practice protocol in our center. Material and Methods A consecutive series of the most recent 80 carotid endarterectomy patients (November 2015–August 2017) treated with the new regime (clopidogrel monotherapy) were compared with the last 80 (January 2012–November 2015) consecutive patients treated according to the old protocol (acetylsalicylic acid and dipyridamole). The primary endpoint was any major bleeding during surgery or in the first 24 to 72 hours postoperatively. Secondary outcomes within 30 days after surgery included minor (re)bleeding postoperative stroke with persistent or transient neurological deficit, persisting or transient neuropraxia, asymptomatic restenosis or occlusion, (transient) headache. Reporting of this study is in line with the ‘Strengthening the Reporting of Observational Studies in Epidemiology’ statement. Results Although statistical differences were observed, from a clinical perspective both patients groups were comparable. Postoperative hemorrhage requiring reexploration for hemostasis occurred in none of the 80 patients in the group of the clopidogrel monotherapy (new protocol) and it occurred in one of the 80 patients (1%) who was using acetylsalicylic acid and dipyridamole (old protocol). In three patients (4%) in the clopidogrel monotherapy and one patient (1%) in the acetylsalicylic acid and extended release dipyridamole protocol an ipsilateral stroke was diagnosed. Conclusion In this retrospective consecutive series the incidence of postoperative ischemic complications and perioperative hemorrhage after carotid endarterectomy (CEA) seemed to be comparable in patients using clopidogrel monotherapy versus acetylsalicylic acid and extended release dipyridamole for secondary prevention after a cerebrovascular event. This study fuels the hypothesis that short- and midterm complications of clopidogrel and the combination acetylsalicylic acid and extended release dipyridamole are comparable.

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

2011 ◽  
Vol 105 (06) ◽  
pp. 1060-1071 ◽  
Author(s):  
Jin Woo Park ◽  
Ok Cheol Jeon ◽  
Sang Kyoon Kim ◽  
Taslim Al-Hilal ◽  
Kyung-Min Lim ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Deoxycholic Acid ◽  
Oral Absorption ◽  
Metabolic Stability ◽  
Oral Dosage ◽  
Low Molecular Weight ◽  
Therapeutic Effects ◽  
Oral Tablet

SummaryThis study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the antithrombotic effect of the subcutaneously injected LMWH (100 IU/ kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.

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