Alendronate Sodium Tablets Research Articles

Evaluation of Biological Mechanisms of Quanduzhong Capsule for Treating Osteoporosis by Integrating Untargeted Metabolomics and Network Pharmacology

AbstractOsteoporosis (OP) is a metabolic disease characterized by bone formation and resorption disturbances. Quanduzhong Capsule (QDZC) is a common treatment for OP in China; however, the effective components and metabolites of the drug after oral administration remain largely unknown. This study aims to identify the active components, analyze the metabolite changes, and investigate the underlying mechanism against OP. In the study, ovariectomy-induced rat OP model was established, then treated with QDZC. Alendronate sodium tablets (ASTs) were used as a reference drug. The chemical constituents of QDZC were analyzed by UPLC-QTOF-MS (ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry) and network pharmacology. The metabolomics was used to analyze differences in serum metabolites of rats in different groups [Sham, Model, Model + QDZC, and Model + AST] at 4, 8, and 12 weeks. Body weight and bone mineral density (BMD) were assessed. Enzyme-linked immunosorbent assay was used to determine serum levels of Akt, p-Akt, ERK, and p-ERK. Our data suggested 86 different chemicals from QDZC, including nine core compounds. QDZC significantly regulated 25 biomarkers linked to arachidonic acid metabolism and unsaturated fatty acid biosynthesis, and promoted serum expression of Akt, p-Akt, ERK, and p-ERK. QDZC might act by activating PI3K-Akt and MAPK signaling pathways. In addition, QDZC may use arachidonic acid derivatives to inhibit osteoclast generation and bone resorption and enhance calcitriol formation to improve calcium absorption and increase bone mass.

Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol

BackgroundOsteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients.MethodsThis multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed.DiscussionThis trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population.Trial registrationThis trial was registered on clinicaltrials.gov (registration number: NCT04739592).

Anti-osteoporosis effect of Notopterygium incisum Ting ex H. T. Chang extract in rats

Purpose: To investigate the effect of Notopterygium incisum Ting ex H.T. Chang extract (NICE) on ovariectomy-induced osteoporosis in rats.
 Methods: Female Sprague-Dawley rats were randomly assigned to a normal group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with positive control drug alendronate sodium tablets (1.8 mg/kg/week), and OVX with varying NICE doses (45, 90, or 180 mg/kg/day). After rats were subjected to ovariectomy for 4 weeks, alendronate or NICE were administered orally daily for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs of all rats was estimated. The serum hormones estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and serum alkaline phosphatase (ALP), osteocalcin (OC) and telopeptides of collagen type I (CTx) levels of rats were detrmined.
 Results: The results show that NICE dose-dependently inhibited bone mineral density (BMD) reduction of L4 vertebrae and femurs (p < 0.05). Compared with OVX group, serum E2, FSH and LH levels was significantly increased in osteoporosis rats (p < 0.01), but serum ALP, CTx, and OC concentrations were significantly lower (p < 0.05). On the other hand, bone trabeculae in the three NICE groups and nilestriol group were all wider, while the space and connections increased.
 Conclusion: These findings indicate that NICE mitigates OVX-induced osteoporosis in rats, and hence can potentially be developed for the management of osteoporosis.

Clinical observation of Yishen Huoxue decoction(YSHXD) for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage

To observe clinical efficacy of Yishen Huoxue decoction(YSHXD) for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage. From January to June 2016, 69 patients (72 hips) with non-traumatic osteonecrosis of femoral head at early and middle stage were divided into treatment group and control group according to therapeutic methods. In treatment group, there were 35 patients 43 hips, including 15 males and 20 females, aged from 28 to 62 years old with an average of(41.80±11.03) years old, 6 hips were at the stage I, 27 hips were at the stageII, 10 hips were at the stage IIIa according to ARCO classification; and treated by using YSHXD, one dose a day for 12 months. In control group, there were 34 patients 39 hips, including 16 males and 18 females, aged from 31 to 61 years old with an average of (43.35±13.52) years old, 5 hips were at the stage I, 26 hips were at the stageII, 8 hips were at the stage IIIa according to ARCO classification; and treated by using alendronate sodium tablets 70 mg every week for 12 months. Preoperative and postoperative HSS score at 2 weeks were observed and compared, EQ-5D index was used to compare clinical effects. ARCO classification was applied to imaging evaluation, the stage of ARCO over IIIa was considered as end point of observation. The final following-up time and ARCO classification were recorded and performed Kaplan-Meier survival analysis. All patients were followed-up from 26 to 76 months with an average of(43.50±13.26) months. Postoperative Harris score at 2 years in treatment group (84.92±7.56) was higher than that of before treatment (73.58±10.02) (P<0.05), and higher than that of control group(79.61±10.92)(P<0.05), especially the scores of joint function and activity were higher than those of control group(P<0.05). EQ-5D index in treatment group 0.66±0.12 was higher than that of control group 0.59±0.12(P<0.05). Nine hips were collapsed in treatment group at final follow-up, and 10 hips were collapsed in control group, and had no statistical difference between two groups (P>0.05). There was no statistical difference in kaplan-meier survival analysis curves between two groups (P>0.05). There were statistical difference in survival rate between the early, middle ARCO stage and different Harris evaluation. YSHXD for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage has obviously clinical effects, could improve hip joint function, and quality of life, and delay the process of femoral head necrosis collapse.

Effect of &lt;i&gt;Dihuang rougui&lt;/i&gt; decoction on ovariectomyinduced osteoporosis in rats

Purpose: To investigate the effect of Dihuang Rougui Decoction (DRD) on ovariectomy-induced osteoporosis in rats.Methods: Female Sprague-Dawley rats were randomly assigned to a normal group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with positive control drug (alendronate sodium tablets, 1.6 mg/kg/week), and OVX + DRD (75, 150 or 300 mg/kg/day). After the rats were subjected to ovariectomy for 4 weeks, fosamax or DRD were administered daily (orally) for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs of the rats was evaluated. Serum hormones estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and serum alkaline phosphatase (ALP), osteocalcin (OC) and telopeptides of collagen type I (CTx) levels of the rats were determined. The bone tissue morphology of the rats was examined by microscopy.Results: The results show that DRD dose-dependently inhibited bone mineral density (BMD) reduction of L4 vertebrae and femurs (both p < 0.05). DRD significantly increased serum E2, FSH and LH levels (p < 0.05) in the osteoporotic rats, and significantly lowered serum ALP, CTx and OC concentrations, compared to OVX group (p < 0.01). Compared with OVX model group, bone trabeculae in all three DRD groups and nilestriol groups were wider, and the space and connections markedly increased. Furthermore, the medullary cavity reduced in size.Conclusion: These findings indicate that DRD mitigates OVX-induced osteoporosis in rats, and thus, the decoction has a potential for clinical management of osteoporosis patients.Keywords: Dihuang Rougui decoction, Osteoporosis, Ovariectomy, Bone mineral density, Serum bone marker, Bone tissue morphology

Short-term effects of extracorporeal shock wave therapy on bone mineral density in postmenopausal osteoporotic patients.

This study evaluated the short-term effectiveness of extracorporeal shock wave therapy (ESWT) on bone mineral density (BMD). A total of 64 postmenopausal osteoporotic patients were recruited and randomized into 3 groups in 2015. Groups A (n=20) and B (n=21) patients received a single-session of low- or high-energy flux density (EFD) ESWT in the left hip, respectively, whereas group C (n=23) patients served as controls without the ESWT treatment. All patients self-administered alendronate sodium tablets orally for a year. The BMD of the lumbar spine (L2-L4), femoral neck, great tuberosity, and total left hip was measured before ESWT treatment and at 3, 6, and 12months using dual energy X-ray absorptiometry (DEXA). At 12months, the lumbar spine, femoral neck, great tuberosity, and total left hip BMD in all patients had increased (p<0.01). The increase in lumbar spine BMD in group A patients was higher than that in group B patients (p=0.03); other between-group differences were not observed (p=0.73, group A vs. C; p=0.06, group B vs. C). The femoral neck, great tuberosity, and total left hip BMD increases in group B patients were higher than that in either group A or C (p<0.01, group B vs. A; p<0.01, group A vs. C). This study showed that ESWT could efficiently improve the local BMD; relatively, the high dosage was effective.

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax&lt;sup&gt;&amp;reg;&lt;/sup&gt; tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

PurposeThe aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet.Materials and methodsA single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods.ResultsThe average maximum concentrations (Cmax) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR) for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were −0.16 and −0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%.ConclusionThe generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions.

Efficacy and safety of the Bushen Tiaochong recipe combined with alendronate sodium for the treatment of postmenopausal senile degenerative osteoporosis: study protocol and preliminary results of a randomized controlled trial

Background and objectives: Alendronate sodium is a commonly used western medicine for the treatment of osteoporosis, but it has many adverse reactions. The main component of the traditional Chinese medicine, known as the Bushen Tiaochong recipe, is Epimedium brevicornu Maxim. (epimedium). Pharmacological studies have shown that the main active ingredient of Epimedium is icariin. Icariin has an estrogen-like effect, can prevent against bone loss and improve bone strength, and has a definite effect on the treatment of postmenopausal senile degenerative osteoporosis. We hypothesize that the Bushen Tiaochong recipe combined with alendronate sodium will be more effective, as well as safer and more reliable than alendronate sodium alone for the treatment of postmenopausal senile degenerative osteoporosis. Design: A prospective, single-center, randomized, controlled, trial. Methods: Two hundred patients with postmenopausal senile degenerative osteoporosis will be randomly assigned to an observation group and a control group. In the control group, patients will be given alendronate sodium tablets 10 mg/d and calcium carbonate D3 chewable tablets 0.6 g/d. In the observation group, patients will receive the same treatment as the control group and the Bushen Tiaochong recipe, simmering, twice per day (once in the morning and once in the evening). The duration of treatment will be 6 months in both groups. Outcome measures and preliminary results: The primary outcome measure is total efficacy 6 months after treatment in both groups. The secondary outcome measures are Visual Analogue Scale scores for waist and back pain; lumbar spine (L2–4) bone mineral density; serum levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, estradiol, follicle stimulating hormone, luteinizing hormone, interleukin-1, and interleukin-6 before and 6 months after treatment; and incidence of adverse reactions 6 months after treatment. The results of a peliminary experiment including 124 patients with postmenopausal senile degenerative osteoporosis who received the same treatment as in the present study revealed that at 6 months after treatment, the total efficacy, L2–4 bone mineral density, serum levels of calcium and estradiol were higher in the observation group than in the control group (P < 0.05). Visual Analogue Scale scores, serum levels of alkaline phosphatase, osteocalcin, interleukin-1, and interleukin-6 were lower in the observation group than in the control group (P < 0.05). Discussion: We hope to verify that the Bushen Tiaochong recipe combined with alendronate sodium provides better results than alendronate sodium alone for the treatment of postmenopausal senile degenerative osteoporosis. Ethics and dissemination: This trial has been approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval number: QHY1703F). The study protocol will be conducted in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be obtained from all participants. The recruitment of subjects will begin in January 2018. Samples and data will be collected from January to December 2018. Outcome measures will be analyzed in March 2019. This trial will be completed in April 2019. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ONC-17013947).

In vitro Dissolution Method for Alendronate Sodium and Vitamin D3 Tablets Using HPLC with Combination of Refractive Index and Ultraviolet Detectors

Two separate HPLC methods were developed for the In-vitro dissolution of Alendronate sodium and Vitamin D3 tablets using Ultra-violet and Refractive index detection. Dissolution method for the estimation of Alendronate sodium (Method-I) in the fixed dose combination uses High Performance Liquid Chromatogaphy (HPLC) with Refractive Index detector (RID) whereas dissolution method for Vitamin D3 (Method-II) uses HPLC with Ultraviolet detector. Method-I uses Hamilton PRP-X500 (150 x 4.6) mm, 7 µ column with 0.01 % Trifluoro acetic acid in water, pH adjusted to 2.5 as mobile phase at a flow rate of 1.5 mL min−1 with Refractive detector sensitivity of 256. Method-II uses Zorbax SB CN (150 x 4.6) mm, 5 µ column with a mixture of water, methanol and acetonitrile in the ratio of 20:72:8 v/v/v as mobile phase at a flow rate of 1.2 mL min−1 with Ultraviolet (UV) detector wavelength of 266 nm. The method was validated for specificity, linearity, precision, accuracy and robustness as per International Conference on Harmonization (ICH) guidelines. This method is useful for the In-vitro dissolution of Alendronate and Vitamin D3 (Cholecalciferol) tablets during routine analysis in Quality control laboratory.

Effects of exercise combined with alendronate sodium tablets on RANKL/OPG balance and MAPK signaling pathways in ovariectomized rats

Objective To observe the effect of exercise combined with alendronate sodium tablets(Aln)on receptor activator of nuclear factor kappa B ligand(RANKL)/osteoprotegerin(OPG)expression and mitogen-activated protein kinase (MAPK)signaling pathways in ovariectomized(OVX)rats.Methods A total of 90 6-month-old female SD rats were evenly randomized into sham group,OVX group,Aln treatment(OVX+Aln)group,exercise therapy(OVX+EX)group,and Aln combined with exercise treatment(OVX+Aln+EX)group.Eight weeks after ovariectomy,rats in the latter three groups were treated with intragastric 1mg/(kg·d)Aln and/or exercise.After 12weeks of treatment,dual-energy X-ray absorptiometry was used to examine the bone mineral density (BMD)of the left and right femurs.Enzyme-linked immunosorbent assay (ELISA)was used to determine the serum levels of RANKL and OPG.Real-time PCR was used to examine RANKLand OPG mRNA expression in bone tissues.Western blotting analysis was used to examine the phosphorylation of c-Jun N-terminal kinase(JNK),p38 MAPK (p38),extracellular-regulated kinase(ERK),and c-Fos protein expression in bone tissues.Results The following results were observed after 12-week treatment.(1)Compared with sham group,the BMD values of the left and right femurs were significantly decreased in OVX group (P0.05).The serum RANKL level was significantly increased,serum OPG level was significantly decreased,and the RANKL/OPG ratio was significantly increased (all P0.05).The RANKL mRNA expression was significantly increased and OPG mRNA expression was significantly decreased in bone tissues(all P0.05).(2)Compared with OVX group,the BMD values of left and right femurs of OVX+ Aln,OVX+EX and OVX+Aln+EX groups were significantly increased (all P0.05).The serum RANKL level was significantly decreased,serum OPG level was significantly increased,and the RANKL/OPG ratio decreased(all P0.05).The RANKL mRNA expression was significantly decreased,and OPG mRNA expression was significantly increased in bone tissues (all P0.05).(3)The femoral BMD values,serum RANKLand OPG levels,and RANKL and OPG mRNA expression in bone tissues in OVX+Aln+EX group were significantly different from those in OVX+Aln group and OVX+EX group(all P 0.05).(4)Compared with sham group,bone tissue p-JNK and c-Fos expression in OVX group was significantly increased (all P0.05).However,compared with OVX group,bone tissue p-JNK and c-Fos expression in OVX+Aln,OVX+EX and OVX+Aln+EX groups was significantly decreased(all P0.05),and there were no significant differences among the latter three groups.p-p38and p-ERK expression was similar in all groups.Conclusion Exercise combined with Aln can improve the BMD values of left and right femurs in OVX rats,which may be related to the regulation of RANKL/OPG balance and inhibition of JNK phosphorylation and c-Fos expression.

Process Analytical Technology to Understand the Disintegration Behavior of Alendronate Sodium Tablets

Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products.

Clinical outcomes of giant cell tumor of bone treated with bone cement filling and internal fixation, and oral bisphosphonates

Giant cell tumor (GCT) of the bone is a relatively common primary bone tumor. Treatment with simple curettage often results in a high local recurrence rate. Tumor resection and reconstruction with prosthesis or an allograft has a low rate of local recurrence; however, the patient’s native joint function becomes significantly impaired. With the development and usage of aggressive curettage, it is a priority to treat GCT with a method that reduces the local recurrence rate and preserves the native joint. To evaluate the feasibility of treating GCT with aggressive curettage and cement filling using internal fixation and oral bisphosphonates, 16 patients with GCT of the bone located in the distal femur and treated in our department from January 2008 to June 2011, were followed up. The patients had received aggressive curettage, bone cement filling, internal fixation and oral administration of bisphosphonates.There were seven males and nine females in total, with a mean age of 38 years. All patients were carefully assessed prior to surgery in order to determine the integrity of the tumor cavity. Subsequently, patients were treated with aggressive curettage by high-speed burring and cementation with internal fixation, and were administered postoperative oral alendronate sodium tablets (10 mg/day) for two years. The median follow-up time was 25 months. None of the patients were lost to follow-up. No local recurrence or metastasis was observed in the last follow-up. The Enneking limb function score range of the affected limb was 24–29 (average, 26.7). At the last follow-up, all patients exhibited solid fixation without fracture of the subchondral bone in plain radiographs. Based on these data, we suggest that patients with distal femoral GCT may be treated with aggressive curettage and cement filling, with internal fixation and oral bisphosphonates. The advantages of this method are its safety and efficacy. However, the long-term outcomes require further investigation.

A VALIDATED STABILITY INDICATING ION EXCHANGE CHROMATOGRAPHIC METHOD FOR THE QUANTIFICATION OF ALENDRONATE, PHOSPHITE AND PHOSPHATE IN ALENDRONATE SODIUM TABLETS AND ANALYSIS OF IN-VITRO DISSOLUTION SAMPLES

A stability-indicating LC method was developed on ion exchange chromatography equipped with refractive index detector for the quantification of phosphite, phosphate content and assay of alendronic acid in pharmaceutical dosage forms. The isocratic separation was achieved by using Allsep anion (150mm x 4.6mm) 7 µm column with mobile phase containing a 5.3 mM formic acid, pH adjusted to 3.5 with sodium hydroxide solution at a flow rate of 1.2 mL/min. Alendronate sodium was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Alendronate sodium was found to degrade significantly in oxidative stress conditions only. The developed method was extensively validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision and robustness. The developed LC method was successfully applied for analysis of in-vitro dissolution samples of marketed alendronate sodium tablets.

Two-way Crossover Bioequivalence Study of Alendronate Sodium Tablets in Healthy, Non-smoking Male Volunteers under Fasted Conditions

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae(0-t) were 604.24 +/- 348.73 microg and 627.36 +/- 327.99 microg, while the mean R(max) were 193.87 +/- 114.68 microg/h and 202.00 +/- 107.83 microg/h for the test and reference formulations, respectively. The T(max) of the test and reference tablets were 1.26 +/- 0.58 h and 1.26 +/- 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae(0-t) and R(max) of alendronic acid, were between 0.86-1.00 and 0.85-1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.

A case of esophageal ulcer caused by alendronate sodium tablets

A case of esophageal ulcer caused by alendronate sodium tablets

In vitro Disintegration Differences Between Branded and Generic Weekly Alendronate Sodium Tablets (70mg) Available in the United States

To offer citizens with frailty or dementia living in nursing homes or other institutions a less stressful and anxious X-ray examination, a Danish hospital offers to perform the examination in the citizen's residence. This has changed the working procedure for the radiographers performing the examination. The aim of this study was to explore if the radiographers self-perceived competencies have changed whilst working in the mobile X-ray unit and if so, how these competencies are utilised within the department-based medical imaging team.This study had a qualitative design following a hermeneutic approach. Individual semi structured interviews included nine radiographers, four radiographers working in the mobile X-ray unit and five radiographers working exclusively in the medical imaging team.Radiographers who worked in the mobile X-ray unit did acquire new competencies such as better communication and creative positioning skills. All nine participants recognised the advantage of sharing experiences and competencies with colleagues, and recommended a formal forum to do so. They sought opportunities for the use of the mobile X-ray unit to be more widespread within their own region, and within the profession.This study indicates that radiographers working with mobile X-ray unit gained new competencies in communication and positioning, but without spread of new knowledge to colleagues in the medical imaging team.The use of home-based mobile X-ray is a new way to provide health care services and gain new competencies for the radiographers to focus on patient centred care.

In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications

ABSTRACTObjective: The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax).Research design and methods: The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison.Results: The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharma­chemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13–24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14–29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification.Conclusions: The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not adequate to establish similar disintegration characteristics.

Application of a semi-automated 96-well format solid-phase extraction, column-switching, fluorescence detection protocol for the determination of alendronate in human urine samples obtained from a bioequivalence study

In the current study, a semi-automated, 96-well format, solid-phase extraction (SPE), analytical column-switching method for alendronate determination in human urine is developed, validated and applied to a bioequivalence study. The current protocol was a substantial improvement of an existing classical method. A robotic liquid handling system was employed to simplify and reduce the time of sample preparation procedure. Automated SPE was carried out using a 96-well cartridge plate and a vacuum control system. Urine samples were determined by applying a column-switching protocol with fluorescence detection. Analysis time, due to the column-switching procedure, was about half of the conventional LC approach (11.5 min instead of 21 min). The method application required the determination of alendronate in urine samples obtained from 96 healthy volunteers as part of a bioequivalence study of two 70 mg alendronate sodium tablets. All major pharmacokinetic parameters of the bioequivalence study were estimated and reported.

Bioequivalence and pharmacokinetics of 70 mg alendronate sodium tablets by measuring alendronate in plasma

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a 2x2 crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h (AUC(0-7h) was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration (Cmax) and the time to reach Cmax (Tmax) were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed AUC(0-7h) and Cmax, and untransformed Tmax. For the test medication versus the reference medication, the AUC(0-7h) were 87.63 +/- 29.27 vs. 102.44 +/- 69.96 ng x h x mL(-1) and the Cmax values were 34.29 +/- 13.77 vs. 38.47 +/- 24.39 ng x mL(-1), respectively. The 90% confidence intervals of the mean differences of the logarithmic transformed AUC(0-7h) and Cmax values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the U.S. Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: t(1/2), 1.87 +/- 0.62 vs. 1.77 +/- 0.54 h; V/F, 2061.30 +/- 986.49 vs. 2576.45 +/- 1826.05 L; CL/F, 835.32 +/- 357.35 vs. 889.48 +/- 485.87 L x h(-1); K(el), 0.42 +/- 0.14 vs. 0.40 +/- 0.18 h(-1); Ka, 4.46 +/- 3.63 vs. 3.80 +/- 3.64 h(-1); and Tlag, 0.19 +/- 0.09 vs. 0.18 +/- 0.06 h. These results indicated that two alendronate formulations (70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

Esophageal irritation due to alendronate sodium tablets: possible mechanisms.

Animal studies were done using an in vivo dog model to examine the possible mechanism for the esophageal adverse events reported with alendronate sodium tablets. These studies showed that under low pH conditions alendronate sodium can cause esophageal irritation. No esophageal irritation occurred at pH 3.5 or higher where the drug exists primarily as the sodium salt. The animal studies also showed that alendronate sodium can exacerbate preexisting esophageal damage. Exposure of the esophageal mucosa for a prolonged period to alendronate sodium tablet can also cause mild esophageal irritation. These findings suggest that the esophageal irritation in patients taking Fosamax can be from prolonged contact with the tablet, reflux of acidic gastric contents with alendronate sodium, and exacerbation of preexisting esophageal damage. The findings also suggest that other bisphosphonates can cause esophageal injury under similar conditions.