Volume 18, Issue 1, Summer 2021, Page 1-105


Paracetamol/ naproxen co-crystals; a simple way for improvement of flowability, tableting and dissolution properties

Amal Al-Dulaimi; Myasar Al-kotaji; Faris Abachi

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 1-19
DOI: 10.33899/iphr.2021.168798

Background: The poor solubility of drugs is one of the most important limitations in formulating drugs into suitable dosage forms. In addition, the mechanical properties are the main obstacles in formulating tablet dosage form by direct compression method. This study aims to investigate the possible improvement in mechanical properties, solubility performance, and tableting properties of drug-drug co-crystals of paracetamol and naproxen. Material and Methods: The three paracetamol/naproxen co-crystals investigated the pre-compression parameters (Angle of repose, Carr’s index, and Hausner’s ratio) of the three paracetamol/naproxen co-crystals were investigated. Moreover, the solubility of the co-crystals was tested as well. In addition, the three paracetamol/naproxen co-crystals were formulated as oral tablets by direct compression method using microcrystalline cellulose and magnesium stearate. The prepared co-crystals were compressed into tablet dosage forms and the dissolution profiles were monitored. Results: The results showed an enhancement in flowability and compressibility of the prepared co-crystals when compared with paracetamol or naproxen alone. The poor tableting properties of prepared paracetamol tablets were very clear and it is in opposite to the co-crystals prepared tablets, which met all the pharmacopeial requirements. The in vitro dissolution study was conducted to compare the dissolution profiles of the prepared co-crystals tablets with marketed paracetamol tablets (Piodol®) and marketed naproxen tablets (Napron®). The dissolution profile of (1 to 2) co-crystal prepared tablets showed a superior dissolution rate with more than 50 % of the paracetamol drug dissolved within the first 5 minutes of dissolution rate. The dissolution study resulted in a better dissolution of the prepared paracetamol/naproxen tablets due to the co-crystal formation. Conclusion: It could be concluded that the prepared paracetamol/naproxen co-crystals represent a promising way for improving flowability and compression properties, enabling the formulation of the co-crystals as oral tablets by direct compression method with a clear enhancement in the dissolution rate.

Impact of Selenium on Structural Changes Induced by Hypothyroidism In Adult Male Rat ׳s Testis

Eman Alhealy; Maysoon Alqazzaz; Wahda M. AL-Nuaimy

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 20-32
DOI: 10.33899/iphr.2021.168799

Background: The poor solubility of drugs is one of the most important limitations in formulating drugs into suitable dosage forms. In addition, the mechanical properties are the main obstacles in formulating tablet dosage form by direct compression method. Aim of this research: To investigate the possible improvement in mechanical properties, solubility performance, and tableting properties of drug-drug co-crystals of paracetamol and naproxen. Methods: The pre-compression parameters (Angle of repose, Carr’s index, and Hausner’s ratio) of the three paracetamol/naproxen co-crystals were investigated. Moreover, the solubility of the co-crystals was tested as well. In addition, the three paracetamol/naproxen co-crystals were formulated as oral tablets by direct compression method using microcrystalline cellulose and magnesium stearate. The prepared co-crystals were compressed into tablet dosage forms and the dissolution profiles were monitored. Results: The results showed an enhancement in flowability and compressibility of the prepared co-crystals when compared with paracetamol or naproxen alone. The poor tableting properties of prepared paracetamol tablets were very clear and they are in opposite to the co-crystals prepared tablets, which met all the pharmacopeial requirements. The in vitro dissolution study was conducted to compare the dissolution profiles of the prepared co-crystals tablets with marketed paracetamol tablets (Piodol®) and marketed naproxen tablets (Napron®). The dissolution profile of (1 to 2) co-crystal prepared tablets showed a superior dissolution rate with more than 50 % of the paracetamol drug dissolved within the first 5 minutes of dissolution rate. The dissolution study resulted in a better dissolution of the prepared paracetamol/naproxen tablets due to the co-crystal formation. Conclusion: It could be concluded that the prepared paracetamol/naproxen co-crystals represent a promising way for improving flowability and compression properties, enabling the formulation of the co-crystals as oral tablets by direct compression method with a clear enhancement in the dissolution rate.

Preparation of Cinnarizine Oral Lyophilizates

Rasha Dhahir; Myasar Al-Kotaji

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 33-43
DOI: 10.33899/iphr.2021.168800

Background: Orally disintegrating tablets (ODTs) have gained an increasing interest in the pharmaceutical industry for the last years. Several technologies have been sophisticated for ODTs to improve patient compliance. In the present work, an attempt has been made to formulate and evaluate cinnarizine, a drug for motion sickness, in an easy to administer, rapid disintegrated dosage form (oral lyophilizates with enhanced disintegration and dissolution profile and consequent potential improvement in bioavailability.
Materials and Methods: Cinnarizine oral lyophilizates were prepared by dispersing the drug in an aqueous solution of mannitol, hydroxypropyl methyl cellulose, and glycine. Different formulations were prepared by freeze-drying (lyophilisation) technique. The effect of concentration of mannitol, hydroxypropyl methyl cellulose, and freezing time on the lyophilizates characteristics was investigated. The drug-excipient interaction was investigated as well.
Results: The resulting cinnarizine oral lyophilizates showed an enhanced disintegration (27.5±3.53 sec to 56±12.73 sec) and enhanced dissolution profile (25.09% to 44.7% after two minutes). The infrared spectroscopic studies showed no drug-excipient interactions. Furthermore, increasing the concentration of mannitol, increasing the concentration of hydroxypropyl methyl cellulose and duplication of the duration of freezing time had a negative influence on the disintegration and dissolution properties of the resulting lyophilizates.
Conclusion: Cinnarizine oral lyophilizates were successfully prepared and resulted in a rapid disintegration, high dissolution profile, with stable characteristics and without noticeable drug-excipient interaction.

Effect of antibiotic misuse on the emergence of microbial resistance among urologic patients

Maimonah Qasim Yahya; Salah H. Azba; Maali I. Al-Hayali

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 44-56
DOI: 10.33899/iphr.2021.168843

Background: The study aimed to identify the types of bacteria isolated from the urine of patients with urinary tract infections focusing on the resistant isolates then comparing the results with the types of antibiotics misused by those patients in order to suggest some measures to mitigate the increasing rates of antibiotic resistance. Material and Methods: Urine samples were collected from patients aged from 10 to 60 years old who visited Al-Jomhory Hospital in Mosul City/Nineveh Governorate during a period between February and May 2021. Bacterial culture, identification, and antimicrobial susceptibility testing against different antibiotics were performed by Kirby Bauer's disc diffusion method and the results were compared with patient medical history of antibiotic use without consulting a physician. Results: Overall, 7 different bacterial pathogens were identified, 5 gram-negative and 2 gram-positive bacteria. The majority of bacterial pathogens isolated was Escherichia coli 37.6%, followed by Klebsiella spp. 35.5%. It is worth noting that the most effective drug was quinolone (P≤ 0.05) on bacterial species with least effective was penicillins worrisome results was the isolation of a high percentage of Pseudomonas aeruginosa, that was resistant to all antibiotics used in this research, by contrast, a high percentage of Enterococcus faecalis was sensitive to those antibiotics. Conclusion: The study revealed that a higher percentage of resistant bacteria were isolated in patients with a medical history of antibiotics misuse which might change drug prescribtion line in a hospitalized patients with bacterial infections.

The Relationship Between Magnesium Supplementation and Glycemic Control in Diabetic Patients: A Review

Doaa K. Ibrahim; Zeina A. Al-Thanoon

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 57-66
DOI: 10.33899/iphr.2021.168801

Background: Diabetes mellitus is a chronic disease with increasing worldwide prevalence. There are many studies to observe the role of minerals on the glycemic state in diabetic patients. One of the in the human se minerals is magnesium. Magnesium is the fourth most abundant mineral in the human body. It has a role in the action of more than 300 enzymes most of them is ATP-dependent reactions. Finally, magnesium has an effect on glucose metabolism, lipid metabolism, nucleic acid synthesis, and energy production. The relationship between magnesium and DM is complex and multifactorial. There is an association between hypomagnesemia and insulin resistance by affecting phosphorylation of insulin receptors, insulin signaling and insulin action. Another consequence of hypomagnesemia is oxidative stress which is also present in the pathogenesis of DM. Objective: This work is trying to emphasize the important role of magnesium in the control of the glycemic state in diabetic patients through highlighting the studies conducted to correlate between magnesium level in the body, dietary magnesium intake, or magnesium supplementation with risk of diabetes mellitus occurrence, insulin sensitivity or glycemic control in diabetic patients. This article suggested that magnesium therapy may be beneficial in improving the clinical parameters of diabetic patients including HbA1c%, fasting serum glucose, and fasting insulin level. 

The Role of Co-Enzyme Q10 in The Respiratory Chain and Some of Its Clinical Indications: A review

Noor Al-Huda A. Al-Zarqy; Zeina A. Al-Thanoon

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 67-77
DOI: 10.33899/iphr.2021.168802

Background: The usage of supplements becomes an important part of everyone health since many of these materials have produced real improvement in general health. These materials are not approved by organization like Food and Drug Administration in the US and the Food Safety Authority in Europe as drugs but their usage as supplement are approved globally. The supplements that will discuss in this review is co-enzyme Q10. It is a potent antioxidant and an essential part of respiratory chain. It acts as a mobile electron carrier between respiratory complexes. When co-enzyme Q10 transfer electron in the oxidative system, it acts to transport proton out of the mitochondria and this produce concentration gradient across membrane. Proton returns inside by enzymatic machine which involved ATP synthesis. Co-enzyme Q10 is the third wide-world used supplement. There are many studies confirm it benefit in many clinical conditions. These include the cardiovascular system, protection against statin induces myopathy, diabetes, neurodegenerative disease in addition to improvement in liver functions. These benefits occurred mainly due to its antioxidant effect and electron scavenging ability which result in reducing oxidative stress and related cell and tissue damage.
Objective This study tries to show the important role of coenzyme Q10 in energy production and spots the light toward the main clinical application of this supplement. Coenzyme Q10 is one of the main elements in the respiratory chain and it is endogenously synthesis since its presence is essential for life. Its availability may reduce in many disease conditions so supplementation of it within diet may become important in management of various disorders.

Strategies To Enhance Transdermal Drug delivery

Mais S. Saadallah; Omar A. Hamid

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 78-92
DOI: 10.33899/iphr.2021.168803

Background: Transdermal drug delivery system (TDDS) is a promising delivery system that provides controlled drug release at a predetermined time. It has many advantages such as bypassing first-pass effect, increase patient convenience by providing single application rather than multiple dosing frequencies, and extends the action of short half-life drugs. There are three ways for drug penetration into the skin either via appendageal (shunt routes), intracellular route, and intercellular route. Permeation of drug substances through the stratum corneum remains a great challenge because it is the rate-limiting step for permeation for most molecules. Aim: This review article highlights the advances and limitations of the strategies to enhance transdermal delivery of the drugs into the skin, including both physical and chemical methods. Conclusion: The transdermal drug delivery system represents a good alternative for oral and parenteral therapy. Various penetration enhancing strategies have been successfully employed to enhance the permeation of low molecular weight molecules. For high molecular weight molecules, physical strategies such as microneedles can be used.
 

Nose to brain delivery of drugs for CNS diseases

Zahraa H. Ali; Myasar Alkotaji

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 93-107
DOI: 10.33899/iphr.2021.168804

Background: The management of central nervous system diseases is extremely challenging due to the numerous obstacles that stand against the successful delivery of drugs to their target site in the brain. Defeating the blood-brain barrier is considered the most significant challenge in this delivery. Different alternative routes of administration have been investigated. Nasal delivery is one of the possible ways for direct brain targeting. The nasal mucosa is the only part of the body at which the external environment become in straight connection with the central nervous system which takes place through the olfactory portion of the nasal mucosa. Different mechanisms have been suggested to describe the pathway for straight nasal to brain transport of medications, however, the precise route is still vague. The most important proposed pathways include nerve pathways (olfactory and trigeminal nerve), vascular, lymphatic, and cerebrospinal fluid mediated pathways. Among these mechanisms, the olfactory intra-neuronal delivery is the dominant one. Various particulate systems have been investigated for nasal delivery with the intention of direct transport to the brain. The most frequently studied delivery systems are polymeric nanosystems, lipid based nanosystems, and nanometric emulsions. In conclusion, direct nasal-to-brain delivery is a very fertile research area and any achievements in this area are running side by side with the progressions that occur in the particulate systems.

A review of the effect of Coenzyme Q10 in patients with polycystic ovary syndrome

Shahad A. Badr; Zeina A. Althanoon

Iraqi Journal of Pharmacy, 2021, Volume 18, Issue 1, Pages 108-117
DOI: 10.33899/iphr.2021.168805

Background: Women with polycystic ovary syndrome are usually suffering from many metabolic disturbances as insulin resistance, so the use of Co enzyme Q10 in those patients improve metabolic changes and insulin resistance resulting in better ovulation.
Mitochondrial dysfunction in the eggs is related to reduction in the oxidative phosphorylation which leads to lower ATP production by mitochondria, also results in deprived reproductive performance, including poor oocyte quality, lessened ovarian store, abnormal conception and unbalanced embryo development.
Objective: The aim of this review is to observe the effects of co enzyme Q10 in PCOS patients by emphasizing many studies that showing the effect of CoQ10 on the metabolic parameters such as (Fasting serum glucose, HbA1c%, total cholesterol, LDL, HDL and triglyceride level).
This article suggested that CoQ10 therapy possess beneficial effect in improving the clinical parameters of PCOS patients including HbA1c%, fasting serum glucose and lipid profile parameters.