Multimodal Pain Management in Orthopedic Surgery.

BACKGROUND: Orthopedic surgery typically results in moderate to severe pain in a majority of patients. Opioids were traditionally the primary medication to target mechanisms of pain transmission. Multimodal analgesia has become a preferred method of pain management in orthopedic practice. Utilizing more than one mode to address post-surgical pain by recruiting multiple receptors through different medications accelerates the recovery process and decreases the need for opioids. By implementing effective analgesic techniques and interventions, this practice, in turn, decreases the usage of perioperative opioids, and in the long term, prevents addiction to pain medications and risk of opioid overdose. In orthopedic surgeries, previous studies have found that multimodal analgesia has reduced early opioid usage in the postoperative course. Pain is the result of direct injury to the nervous system, with a wide variety of chemicals directly stimulating or sensitizing the peripheral nociceptors. The pathophysiology behind the mechanism of post-surgical pain, along with the importance of preoperative, perioperative, and postoperative pain regimens are emphasized. A brief overview of pain medications and their properties is provided. These medications are further categorized, with information on special considerations and typical dosage requirements. Pain management should address both neuropathic and subjective types of pain. Effective pain control requires constant reassessment with individualized strategies. CONCLUSION: By focusing on multimodal analgesia, anesthesiologists can now utilize newer techniques for postoperative pain relief from orthopedic surgery, with better short-term and long-term outcomes for the patient.

Fast-dissolving and high-drug-loaded, Fatty Acid-based self-emulsifying solid dispersions of diacerein.

The purpose of the present study was to enhance the solubility and dissolution of diacerein by preparing their fatty acid-based, self-emulsifying solid dispersions (SDs) containing polyethylene glycol 6000 (PEG 6000), surfactant, and self-emulsifying excipient with high drug content. Ternary and self-emulsifying SDs containing high drug content were prepared and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy, solubility studies, and dissolution studies. When hydrophilic and lipophilic excipients were combined and incorporated into PEG 6000-based SDs, a remarkable enhancement of the dissolution rate was observed, even in SDs with high drug content. The presence of surfactant and self-emulsifying excipient did not affect the solid state characterization of the drug. The decrease in the intensity of the numerous distinctive peaks of the drug in the PXRD spectra and absence of drug melting peak in DSC spectra demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix. The utilization of self-emulsifying excipient and surfactant in PEG 6000-based SDs could be a useful tool to enhance the dissolution and bioavailability of diacerein by forming solubilizing and microemulsifying systems with high drug content. LAY ABSTRACT: The purpose of the present study was to enhance the solubility and dissolution of diacerein by preparing their fatty acid-based, self-emulsifying solid dispersions with high drug content. These solid dispersions were prepared and characterized by powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, solubility studies, and dissolution studies. When hydrophilic and lipophilic excipients were combined and incorporated into PEG 6000-based solid dispersions, a remarkable enhancement of the dissolution rate was observed, even in solid dispersions with high drug content. Moreover, the presence of surfactant and self-emulsifying excipient did not affect the solid state characterization of the drug. The decrease in the intensity of the numerous distinctive peaks of the drug in the powder X-ray diffraction spectra and absence of drug melting peak in the spectra obtained by differential scanning calorimetry demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix.

Solubility and solution stability studies of different amino acid prodrugs of bromhexine.

OBJECTIVE: The aim of the present study was to prepare the amino acid prodrugs of bromhexine hydrochloride to improve its solubility. METHODS: All the prodrugs were synthesized by first reacting bromhexine with tert-butoxycarbonyl (Boc) protected amino acid and then deprotection was carried out by using trifluoroacetic acid. These prodrugs were characterized by their melting points, NMR, mass and FTIR spectroscopy. Solubility and partition coefficient of bromhexine and various prodrugs were determined. The solution stability of various prodrugs was also determined in various buffers of pH ranging from 2 to 10. Degradation rate constants and half-life were also determined at various pH. RESULTS AND DISCUSSION: The structures of all the synthesized prodrugs were confirmed by NMR, mass and FTIR spectra. The prodrug 2-N-L-alanyl-bromhexine hydrochloride showed maximum solubility and minimum partition coefficient value. These prodrugs may hydrolyze by one or more mechanisms. The order of decreasing rates of hydrolysis was 2-N-L-prolyl-bromhexine hydrochloride > 2-N-glycyl-bromhexine hydrochloride > 2-N-L-alanyl-bromhexine hydrochloride. All the prodrugs exhibited maximum stability in the acidic pH range and undergo base catalyzed hydrolysis. CONCLUSION: Solubility studies and partition coefficient values indicated that the synthesized prodrug, 2-N-L-alanyl-bromhexine hydrochloride, was least lipophilic as compared to other synthesized prodrugs. Solution stability studies showed that this prodrug undergo minimum hydrolysis at 37°C. So, it is concluded that 2-N-L-alanyl-bromhexine hydrochloride exhibits better solubility and stability as compared to other synthesized prodrugs.

Physicochemical characterization and dissolution study of solid dispersions of ketoconazole with nicotinamide.

PURPOSE: The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug ketoconazole using solid dispersion technique. METHODS: Solid dispersions of ketoconazole were prepared in ratios of 90 : 10, 70 : 30, 50 : 50, 30 : 70 and 10 : 90 by the melting method using nicotinamide as carrier. These solid dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy to ascertain if there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure ketoconazole, physical mixtures and solid dispersions. RESULTS: Solubility studies indicated that nicotinamide increased significantly the solubility of ketoconazole in water. The Gibbs free energy (ΔG°(tr)) values were negative indicating the spontaneous nature of ketoconazole solubilization, and it decreased with increase in concentration of the carrier, demonstrating that the reaction became more favorable as the concentration of the carrier increased. The cumulative release of ketoconazole within 120 min from solid dispersion at a drug-to-nicotinamide ratio of 10 : 90 (w/w) was 6 times higher than the pure drug in phosphate buffer of pH 6.8. CONCLUSION: Solid state characterization indicated that there is no interaction between ketoconazole and nicotinamide in the solid state. In contrast to the very slow dissolution rate of pure ketoconazole, the dispersion of the drug in nicotinamide considerably enhanced the dissolution rate. The drug dissolution rate was highest at a drug-to-nicotinamide ratio of 10 : 90 (w/w).

Physicochemical characterization and dissolution study of solid dispersions of diacerein with polyethylene glycol 6000.

OBJECTIVE: Diacerein (DCN) is a new anti-inflammatory analgesic and antipyretic drug developed specially for the treatment of osteoarthritis. DCN is a poorly water-soluble drug with relatively low bioavailability. Therefore, the purpose of this study was to enhance the solubility and dissolution of DCN by complexation with polyethylene glycol 6000 (PEG). METHODS: Solid dispersions (SDs) of DCN were prepared in weight ratios of 60:40, 40:60, 20:80, and 5:95 by the melting method using PEG as carrier. These SDs were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy to ascertain whether there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure DCN, physical mixtures (PMs) and SDs. RESULTS AND DISCUSSION: Solubility studies indicated that PEG significantly increased the solubility of DCN in water. The Gibbs free energy (ΔG(tr)°) values were negative, indicating the spontaneous nature of DCN solubilization. Phase solubility studies indicated complex with a possible stoichiometry of 1:1. CONCLUSION: FTIR, DSC and PXRD studies indicate that there is no chemical interaction between DCN and PEG in solid state. In contrast to slow dissolution rate of pure DCN, the dispersion of drug in PEG considerably enhanced the dissolution rate. Even PMs of DCN prepared with PEG also showed better dissolution profiles compared with that of DCN, indicating the solubilization effect of PEG. Therefore, it is concluded that the preparation of SDs of DCN with PEG provides a promising way to increase its solubility and dissolution rate.